",isbn:"978-1-83968-727-3",printIsbn:"978-1-83968-726-6",pdfIsbn:"978-1-83968-728-0",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"625b869ee498e8ac2159ddaf9fb4a906",bookSignature:"Dr. Sonia Soloneski and Dr. Marcelo L. Larramendy",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10368.jpg",keywords:"Biomarkers, Safety Testing, Pesticides, Biomolecules, Medical Devices, Nanomaterials, Drugs, Radiation, Apoptosis, Autophagy, Cytotoxicity Testing, Standardized Procedures",numberOfDownloads:9,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 7th 2020",dateEndSecondStepPublish:"October 5th 2020",dateEndThirdStepPublish:"December 4th 2020",dateEndFourthStepPublish:"February 22nd 2021",dateEndFifthStepPublish:"April 23rd 2021",remainingDaysToSecondStep:"4 months",secondStepPassed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"An Assistant Professor of Molecular Cell Biology at the National University of La Plata (Argentina) that authored more than 380 contributions in the field, including scientific publications in peer-reviewed journals and research communications.",coeditorOneBiosketch:"Head of the Laboratory of Molecular Cytogenetics and Genotoxicology at the National University of La Plata (Argentina) and author of more than 450 contributions, including scientific publications, research communications, and conferences worldwide.A recipient of several national and international awards.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"14863",title:"Dr.",name:"Sonia",middleName:null,surname:"Soloneski",slug:"sonia-soloneski",fullName:"Sonia Soloneski",profilePictureURL:"https://mts.intechopen.com/storage/users/14863/images/system/14863.jpeg",biography:"Sonia Soloneski has a Ph.D. in Natural Sciences and is an Assistant Professor of Molecular Cell Biology at the School of Natural Sciences and Museum of La Plata, National University of La Plata, Argentina. She is a member of the National Scientific and Technological Research Council (CONICET) of Argentina in the genetic toxicology field, the Latin American Association of Environmental Mutagenesis, Teratogenesis, and Carcinogenesis (ALAMCTA), the Argentinean Society of Toxicology (ATA), the Argentinean Society of Genetics (SAG), the Argentinean Society of Biology (SAB), and the Society of Environmental Toxicology and Chemistry (SETAC). She has authored more than 380 contributions in the field, including scientific publications in peer-reviewed journals and research communications. She has served as a review member for more than 30 scientific international journals. She has been a plenary speaker in scientific conferences and a member of scientific committees. She is a specialist in issues related to genetic toxicology, mutagenesis, and ecotoxicology.",institutionString:"National University of La Plata",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"5",institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}}],coeditorOne:{id:"14764",title:"Dr.",name:"Marcelo L.",middleName:null,surname:"Larramendy",slug:"marcelo-l.-larramendy",fullName:"Marcelo L. Larramendy",profilePictureURL:"https://mts.intechopen.com/storage/users/14764/images/system/14764.jpeg",biography:"Marcelo L. Larramendy, Ph.D., serves as a Professor of Molecular Cell Biology at the School of Natural Sciences and Museum (National University of La Plata, Argentina). He was appointed as Senior Researcher of the National Scientific and Technological Research Council of Argentina. He is a former member of the Executive Committee of the Latin American Association of Environmental Mutagenesis, Teratogenesis, and Carcinogenesis. He is the author of more than 450 contributions, including scientific publications, research communications, and conferences worldwide. He is the recipient of several national and international awards. Prof. Larramendy is a regular lecturer at the international A. Hollaender courses organized by the IAEMS and a former guest scientist at NIH (USA) and the University of Helsinki, (Finland). He is an expert in genetic toxicology and is, or has been, a referee for more than 20 international scientific journals. He was a member of the International Panel of Experts at the International Agency for Research on Cancer (IARC, WHO, Lyon, France) in 2015 for the evaluation of DDT, 2,4-D, and Lindane. Presently, Prof. Dr. Larramendy is Head of the Laboratory of Molecular Cytogenetics and Genotoxicology at the UNLP.",institutionString:"National University of La Plata",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"17",institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"6",title:"Biochemistry, Genetics and Molecular Biology",slug:"biochemistry-genetics-and-molecular-biology"}],chapters:[{id:"74835",title:"Some Methodological Aspects in Studies of Metal Nanoparticles’ Toxicity towards Cultured Cells",slug:"some-methodological-aspects-in-studies-of-metal-nanoparticles-toxicity-towards-cultured-cells",totalDownloads:10,totalCrossrefCites:0,authors:[null]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"9699",firstName:"Iva",lastName:"Lipović",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/9699/images/4740_n.png",email:"iva.l@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"874",title:"Integrated Pest Management and Pest Control",subtitle:"Current and Future Tactics",isOpenForSubmission:!1,hash:"f9bb193803d54978099900e0645e2637",slug:"integrated-pest-management-and-pest-control-current-and-future-tactics",bookSignature:"Marcelo L. Larramendy and Sonia Soloneski",coverURL:"https://cdn.intechopen.com/books/images_new/874.jpg",editedByType:"Edited by",editors:[{id:"14863",title:"Dr.",name:"Sonia",surname:"Soloneski",slug:"sonia-soloneski",fullName:"Sonia Soloneski"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3801",title:"Pesticides",subtitle:"Toxic Aspects",isOpenForSubmission:!1,hash:"e0e479dbebe7f25ae49495b3d6d22eb2",slug:"pesticides-toxic-aspects",bookSignature:"Marcelo L. Larramendy and Sonia Soloneski",coverURL:"https://cdn.intechopen.com/books/images_new/3801.jpg",editedByType:"Edited by",editors:[{id:"14863",title:"Dr.",name:"Sonia",surname:"Soloneski",slug:"sonia-soloneski",fullName:"Sonia Soloneski"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2035",title:"Insecticides",subtitle:"Basic and Other Applications",isOpenForSubmission:!1,hash:"a1a58545e043b9616c972a9eed86b0f1",slug:"insecticides-basic-and-other-applications",bookSignature:"Sonia Soloneski and Marcelo Larramendy",coverURL:"https://cdn.intechopen.com/books/images_new/2035.jpg",editedByType:"Edited by",editors:[{id:"14863",title:"Dr.",name:"Sonia",surname:"Soloneski",slug:"sonia-soloneski",fullName:"Sonia Soloneski"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3521",title:"Weed and Pest Control",subtitle:"Conventional and New Challenges",isOpenForSubmission:!1,hash:"66ed4d91a67af8b180cb863d339021c1",slug:"weed-and-pest-control-conventional-and-new-challenges",bookSignature:"Sonia Soloneski and Marcelo Larramendy",coverURL:"https://cdn.intechopen.com/books/images_new/3521.jpg",editedByType:"Edited by",editors:[{id:"14863",title:"Dr.",name:"Sonia",surname:"Soloneski",slug:"sonia-soloneski",fullName:"Sonia Soloneski"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6644",title:"Emerging Pollutants",subtitle:"Some Strategies for the Quality Preservation of Our Environment",isOpenForSubmission:!1,hash:"9e03aeca8b09510ef11fcf3621a2a996",slug:"emerging-pollutants-some-strategies-for-the-quality-preservation-of-our-environment",bookSignature:"Sonia Soloneski and Marcelo L. Larramendy",coverURL:"https://cdn.intechopen.com/books/images_new/6644.jpg",editedByType:"Edited by",editors:[{id:"14863",title:"Dr.",name:"Sonia",surname:"Soloneski",slug:"sonia-soloneski",fullName:"Sonia Soloneski"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6694",title:"New Trends in Ion Exchange Studies",subtitle:null,isOpenForSubmission:!1,hash:"3de8c8b090fd8faa7c11ec5b387c486a",slug:"new-trends-in-ion-exchange-studies",bookSignature:"Selcan Karakuş",coverURL:"https://cdn.intechopen.com/books/images_new/6694.jpg",editedByType:"Edited by",editors:[{id:"206110",title:"Dr.",name:"Selcan",surname:"Karakuş",slug:"selcan-karakus",fullName:"Selcan Karakuş"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"41239",title:"Using Molecular Modelling to Study Interactions Between Molecules with Biological Activity",doi:"10.5772/54007",slug:"using-molecular-modelling-to-study-interactions-between-molecules-with-biological-activity",body:'
1. Introduction
To better understand the basis of the activity of any molecule with biological activity, it is important to know how this molecule interacts with its site of action, more specifically its conformational properties in solution and orientation for the interaction. Molecular recognition in biological systems relies on specific attractive and/or repulsive interactions between two partner molecules. This study seeks to identify such interactions between ligands and their host molecules, typically proteins, given their three-dimensional (3D) structures. Therefore, it is important to know about interaction geometries and approximate affinity contributions of attractive interactions. At the same time, it is necessary to be aware of the fact that molecular interactions behave in a highly non-additive fashion. The same interaction may account for different amounts of free energy in different contexts and any change in molecular structure might have multiple effects, so it is only reliable to compare similar structures. In fact, the multiple interactions present in a single two-molecule complex are a compromise between attractive and repulsive interactions. On the other hand, a molecular complex is not characterised by a single structure, as can be seen in crystal structures, but by an ensemble of structures. Furthermore, changes in the degree of freedom of both partners during an interaction have a large impact on binding free energy [Bissantz et al., 2010].
The availability of high-quality molecular graphics tools in the public domain is changing the way macromolecular structure is perceived by researchers, while computer modelling has emerged as a powerful tool for experimental and theoretical investigations. Visualisation of experimental data in a 3D, atomic-scale model can not only help to explain unexpected results but often raises new questions, thereby affecting future research. Models of sufficient quality can be set in motion in molecular dynamic (MD) simulations to move beyond a static picture and provide insight into the dynamics of important biological processes.
Computational methods have become increasingly important in a number of areas such as comparative or homology modelling, functional site location, characterisation of ligand-binding sites in proteins, docking of small molecules into protein binding sites, protein-protein docking, and molecular dynamic simulations [see for example Choe & Chang, 2002]. Current results yield information that is sometimes beyond experimental possibilities and can be used to guide and improve a vast array of experiments.
To apply computational methods in drug design, it is always necessary to remember that to be effective, a designed drug must discriminate successfully between the macromolecular target and alternative structures present in the organism. The last few years have witnessed the emergence of different computational tools aimed at understanding and modelling this process at the molecular level. Although still rudimentary, these methods are shaping a coherent approach to help in the design of molecules with high affinity and specificity, both in lead discovery and in lead optimisation. Moreover, current information on the 3D structure of proteins and their functions provide a possibility to understand the relevant molecular interactions between a ligand and a target macromolecule. As a consequence, a comprehensive study of drug structure–activity relationships can help identify a 3D pharmacophore model as an aid for rational drug design, as a pharmacophore model can be defined as ‘an ensemble of steric and electronic features that is necessary to ensure the optimal supramolecular interactions with a specific biological target and to trigger (or block) its biological response’, and a pharmacophore model can be established either in a ligand-based manner, by superposing a set of active molecules and extracting common chemical features that are essential for their bioactivity, or in a structure-based manner, by probing possible interaction points between the macromolecular target and ligands.
Molecular recognition (MR) is a general term designating non-covalent interactions between two or more compounds belonging to host-guest, enzyme-inhibitor and/or drug-receptor complexes. A rigorous approach to an MR study should involve the adoption of a computational method independent from the chemical intuition of the researcher. Drug design purposes prompt another challenging feature of such an ideal computational method, the ability to make sufficiently accurate thermodynamic predictions about the recognition process.
2. Molecular modelling methods and their usefulness
Molecular recognition is a central phenomenon in biology, for example, with enzymes and their substrates, receptors and their signal inducing ligands, antibodies and antigens, among others. Given two molecules with 3D conformations in atomic detail, it is important to know if the molecules bind to each other and, if it is so, what does the formed complex look like (“docking”) and how strong is the binding affinity (that can be related to the “scoring”functions).
Molecules are not rigid. The motional energy at room temperature is large enough to let all atoms in a molecule move permanently. That means that the absolute positions of atoms in a molecule, and of a molecule as a whole, are by no means fixed, and that the relative location of substituents on a single bond may vary with time. Therefore, any compound containing one or several single bonds exists at every moment in many different conformers, but generally only low energy conformers are found to a large extent [Kund, 1997, as cited in Tóth et al., 2005].
The biological activity of a drug molecule is supposed to depend on one single unique conformation amongst all the low energy conformations, the search for this so-called bioactive conformation for compound sets being one of the major tasks in Medicinal Chemistry. Searching for all low energy conformations is possible with molecular modelling studies, since molecular modelling is concerned with the description of the atomic and molecular interactions that govern microscopic and macroscopic behaviours of physical systems. These molecular interactions are classified as: (a) bonded (stretching, bending and torsion), (b) non-bonded (electrostatic (including interactions with metals), van der Waals and π-stacking), and (c) derived, as they result from the previous ones (hydrogen bonds and hydrophobic effect).
Protein-ligand or, in general, molecule-molecule binding free energy differences can a priori be computed from first principles using free energy perturbation techniques and a full atomic detailed model with explicit solvent molecules using molecular dynamics simulations. However, these are computationally demanding. More affordable approaches use end-point molecular dynamic simulations and compute free energies accounting for solvent effects with continuum methods, such as MM-PBSA (molecular mechanics Poisson-Boltzman surface area) or MM-GBSA (generalized Born surface area) [Kollman et al., 2000; Wang et al., 2005]. One of the first approaches was comparative molecular field analysis (CoMFA) [Cramer et al., 1988], which enabled interpretation and understanding of enzyme active sites when the crystal structure was absent. However, this type of analysis was not possible until in vitro drug-drug interaction studies were widely used (through the 1990s).
2.1. Molecular mechanics, molecular dynamics and docking
Molecular mechanics (MM) is often the only feasible means with which to model very large and non-symmetrical chemical systems such as proteins and polymers. Molecular mechanics is a purely empirical method that neglects explicit treatment of electrons, relying instead on the laws of classical physics to predict the chemical properties of molecules. As a result, MM calculations cannot deal with problems such as bond breakage or formation, where electronic or quantum effects dominate. Furthermore, MM models are wholly system-dependent. MM energy predictions tend to be meaningless as absolute quantities, as the zero or reference value depends on the number and types of atoms and their connectivity, and so they are generally useful only for comparative studies. A force field is an empirical approximation for expressing structure-energy relationships in molecules and is usually a compromise between speed and accuracy.
Molecular mechanics have been shown to produce more realistic geometry values for the majority of organic molecules, owing to the fact that they are highly parameterised. Parameterisation of structures should be performed with care and non-“standard” molecules will need to have new parameters. This is usually done by analogy for bonded terms and assigning charges by a procedure consistent with the used force field.
There are many levels of theory in which computational models of 3D structures can be constructed. The overall aim of modelling methods is often to try to relate biological activity to structure. An important step towards this goal is to be able to compute the potential energy of the molecule as a function of the position of the constituent atoms. Once a method for evaluating the molecular potential energy is available, it is natural to search for an optimum molecular geometry by minimising the energy of the system. In a biological macromolecule, the potential energy surface is a complicated one, in which there are many local energy minima as well as a single overall energy minimum. All the energy minimisation algorithms commonly used have a marked tendency to locate only a local energy minimum that is close to the starting conformation. For a biological macromolecule, the number of conformations that have to be searched rises exponentially with the size of the molecule; hence, systematic searching is not a practical method for large molecules.
Molecular dynamics (MD) is a conformation space search procedure in which the atoms of a biological macromolecule are given an initial velocity and are then allowed to evolve in time according to the laws of Newtonian mechanics [van Gunsteren & Berendsen, 1977]. Depending on the simulated temperature of the system, the macromolecule can then overcome barriers at the potential energy surface in a way that is not possible with a minimisation procedure. One useful combination of molecular dynamics and minimisation schemes is a method known as simulated annealing [Kirkpatrick et al, 1983, Černý, 1985]. This method uses a molecular dynamics calculation in which the system temperature is raised to a high value to allow for a widespread exploration of the available conformational space. The system temperature is then gradually decreased as further dynamics are performed. Finally, a minimisation phase may be used to select a minimum energy molecular conformation.
One of the most important applications of molecular modelling techniques in structural biology is the simulation of the docking of a ligand molecule onto a receptor. These methods often search to identify the location of the ligand binding site and the geometry of the ligand in the active site, to get the correct ranking when considering a series of related ligands in terms of their affinity, or to evaluate the absolute binding free energy as accurately as possible. To select a force field and the adequate modelling methodology for a given task, it is important to appreciate the range of molecular systems to which it is applicable and the types of simulations that can be performed.
2.2. Most used existing force fields
AMBER (Assisted Model Building with Energy Refinement) developed by Kollman et al. [http://ambermd.org/] was originally parameterised specifically for proteins and nucleic acids [Weiner et al., 1984, 1986; Cornell et al., 1995], using 5 bonding and non-bonding terms along with a sophisticated electrostatic treatment and with no cross terms included. The results obtained with this method can be very good for proteins and nucleic acids, but less so for other systems, although parameters that enable the simulation of other systems have been published [for examples see Doshi & Hamelberg, 2009; Zgarbová et al., 2011].
CHARMM (Chemistry at HARward Macromolecular Mechanics) developed by Karplus et al. [http://www.charmm.org] was originally devised for proteins and nucleic acids [Brooks et al., 1983], and is now used for a range of macromolecules, molecular dynamics, solvation, crystal packing, vibrational analysis and QM/MM (quantum mechanics/molecular mechanics) studies. It uses five valence terms, one of which is electrostatic and is a basis for other force fields (e.g., MOIL [Elber et al., 1995]).
GROMOS (Groningen Molecular Simulation) developed at the University of Groningen and the ETH (Eidgenössische Technische Hochschule) of Zurich [http://www.igc.ethz. ch/GROMOS/index] is quite popular for predicting the dynamical motion of molecules and bulk liquids, also being used for modelling biomolecules. It uses five valence terms, one of which is electrostatic [van Gunsteren and Berendsen., 1977]. Its parameters are currently being updated [Horta et al., 2011].
MM1-4 (Molecular Mechanics) developed by Allinger [1976] are general purpose force fields for monofunctional organic molecules. The first version of this method was the MM1 [Allinger, 1976]. MM2 was parameterised for a lot of functional groups while MM3 [Allinger & Durkin, 2000; Allinger & Yan, 1993] is probably one of the most accurate ways of modelling hydrocarbons. MM4 is the latest version with several improvements [Allinger et al., 1996].
MMFF (Merck Molecular Force Field) developed by Halgren [1996] is also a general purpose force field mainly for organic molecules. MMFF94 [Halgren, 1996] was originally designed for molecular dynamics simulations, but has also been widely used for geometrical optimisation. It uses five valence terms, one of which is electrostatic and another is a cross term. MMFF was parameterised based on high level ab initio calculations. MMFF94 contains parameters for a wide variety of functional groups that arise in Organic and Medicinal Chemistry.
OPLS (Optimized Potential for Liquid Simulations) developed by Jorgensen at Yale [http://zarbi.chem.yale.edu] was designed for modelling bulk liquids [Jorgensen & Tirado-Rives, 1996] and has been extensively used for modelling the molecular dynamics of biomolecules. It uses five valence terms, one of which is an electrostatic term and none of them is a cross term.
TRIPOS (Sybil force field) is a commercial method designed for modelling organics and biomolecules. It is often used for CoMFA analysis and uses five valence terms, one of which is an electrostatic term.
CVFF (Consistent Valence Force Field) developed by Dauber-Osguthorpe is a method parameterised for small organic (amides and carboxylic acids, among others) crystals and gas phase structures [Dauber-Osguthorpe et al., 2004]. It handles peptides, proteins and a wide range of organic systems. It was primarily intended for studies of structures and binding energies, although it predicts vibrational frequencies and conformational energies reasonably well.
2.3. Popular docking programs
One of the most important and useful areas of application of molecular modelling is the approach of docking a protein onto a second molecule, typically a small ligand. This is of interest because it models the possible interactions between the protein and the ligand in the formation of a biologically important protein-ligand complex. To perform a computational docking, experimental or model 3D structures of both the protein and ligand molecules are required together with the charge distribution for each molecule.
There are several software programs that are available for carrying out docking calculations, only some of them will be considered here. The DOCK program suite [Kuntz, 1992] is one of the best known. First of all, a set of overlapping spheres are used in the program to construct a negative image of a specified site on the protein or another macromolecule, and the negative image is then matched against structures of potential ligands. Matches can be scored in this program by the quality of the geometric fit, as well as by the molecular mechanics interaction energy [Meng et al., 1992] and can lead to protein-binding ligands that have micromolecular levels of binding affinity [Kuntz et al., 1994]. It has also been used for modelling protein-protein docking [Shoichet & Kuntz, 1996].
The program GRID [Goodford, 1985] identifies likely protein binding sites for ligands [Reynolds et al., 1989; Cruciani & Goodford, 1994] using a 3D grid around the protein.
The program AutoDock developed by Morris et al.; [http://www.scripps.edu/pub/olson-web/doc/autodock/] uses a grid-based scheme for energies of individual atoms, allowing a quick computation of the interaction energy of the protein-ligand complex as the interaction between the ligand and the grid.
GLIDE software [Friesner et al., 2004, 2006; Halgren et al., 2004] also uses a grid-based scheme to represent the shape and properties of the receptor and then uses a systematic search algorithm to produce a set of initial conformations, using a OPLS-AA force field for ligand minimisation in the field of the receptor.
SURFLEX [Jain, 2003, 2007] is a fully automatic flexible molecular docking algorithm that presents results evaluated for reliability and accuracy in comparison with crystallographic experimental results on 81 protein/ligand pairs of substantial structural diversity.
In a recent study, comparison of seven popular docking programs [Plewczynski et al., 2011] clearly showed that the ligand binding conformation could be identified in most cases by using the existing software. Yet, there is still the lack of universal scoring function for all types of molecules and protein families. One can always hope that incremental improvements in current techniques will gradually lead to major advances in this field.
3. The solvent and how to model it
Solvation plays an important role in ligand-protein association and has a strong impact on comparisons of binding energies for dissimilar molecules. The binding affinity of a ligand for a receptor (ΔGbind) depends on the interaction free energy of the two molecules relative to their free energy in solution:
ΔGbind = ΔGinteract – ΔGsolv,L - ΔGsolv,R\n\t\t\t
where ΔGinteract is the interaction free energy of the complex, ΔGsolv,L is the free energy of desolvating the ligand, and ΔGsolv,R is the free energy of occluding the receptor site from the solvent. Various methods have been proposed to evaluate or estimate these terms. The problem is difficult because the energy of each component on the right hand side of Equation 1 is large while the difference between them is small.
An accurate way to calculate relative binding energies is with free-energy perturbation techniques, although they are usually restricted to calculating the differential binding of similar compounds and require extensive computation, making it impractical as an initial screen, but quite useful sometimes [Buch et al., 2011; Reddy & Erion, 2007]. Several authors have described force fields that consider the bound and solvated states [see for example Chen et al., 2008; Moon & Howe, 1991], successfully predicting new ligands and also the structures of ligand-receptor complexes [Wilson et al., 1991].
When calculating interactions in congeneric series, the cost in electrostatic free energy of desolvating both the enzyme binding site and the burial part of the ligand (ΔGdesolv) is roughly constant within the series. This is particularly true when the calculation is done partitioning the electrostatic free energy contributions into a van der Waals term from the molecular mechanics force field, and an electrostatic contribution computed using a continuum method [Checa et al., 1997]. For that reason, it has been proposed to neglect ΔGdesolv in earlier studies.
The binding energy between ligand and receptor is approximated to the interaction enthalpy calculated by means of empirical energy functions that represent van der Waals repulsion, dispersion interactions by a Lennard-Jones term, and electrostatic interactions in the form of a Coulomb term that uses atom-centred point charges [Ajay & Murcko, 1995]. In most cases, these calculations of molecular mechanics are performed on a structure that is taken to represent the ensemble average of each complex. Entropy contributions are usually ignored although solvation terms are sometimes added to the scoring function by calculating changes in buried nonpolar surface area [Viswanadhan et al., 1999] or differences in the ease of desolvation of both the ligand and the binding site upon complex formation [Checa et al., 1997]. Molecular mechanics-based QSAR studies on ligand-receptor complexes can benefit greatly from proper incorporation of solvation effects into a COMBINE framework based on residue-based interaction energy decomposition [Pérez et al., 1998].
The relevance of solvation in modulating the biological activity of drugs is well known [Orozco & Luque, 2000]. In the last years, theoretical methods have been developed to calculate fragment contributions to the solvation free energy, particularly in the framework of quantum mechanical (QM) continuum solvation methods [Klamt et al., 2009]. Thus, fractional methods based on GB/SA methods have been developed [Cramer & Truhlar, 2008], as well as those based on the MST(Miertus-Scrocco-Tomasi) solvation method model [Soteras et al., 2004].
An explicit solvent model includes individual solvent molecules and calculates the free energy of solvation by simulating solute-solvent interactions. It requires an empirical interaction potential between the solvent and the solute, and between the solvent molecules, usually involving Monte Carlo (MC) calculations and/or molecular dynamics. MC calculations can be used to compute free energy differences and radial distribution functions, among others, and cannot be used to compute time-dependent properties such as diffusion coefficients or viscosity. MD simulations, on the other hand, can be used to compute free energies and time-dependent properties, transport properties, correlation functions, and others.
An implicit solvent model treats solvent as a polarisable continuum with a dielectric constant, ε, instead of explicit solvent molecules. The charge distribution of the solute polarises the solvent, producing a reaction potential that alters the solute. This interaction is represented by a solvent reaction potential introduced into the Hamiltonian. As interactions should be self consistently computed, they are also known as self-consistent reaction field (SCRF) methods [Onsager, 1936]. These models are significantly easier than explicit solvent models, but cannot model specific interactions such as hydrogen bonds.
Changes in hydration free energy during complex formation are a crucial element of binding free energies [Gilson & Zhou, 2007]. With the use of methods to predict binding free energies becoming common-place in the field of drug design, there is still a need for solvation methods that are both quick and accurate [Mancera, 2007], although much research has been carried out on the improvement of existing methods and development of new solvation models at many levels of theory [Chambers et al., 1996; Gallicchio et al., 2002; Palmer et al., 2011].
Explicit solvation models such as free energy perturbation (FEP), thermodynamic integration (TI) [Gilson & Zhou, 2007; Khavertskii & Wallquist, 2010] and the faster linear interaction energy (LIE) [Aqvist et al., 1994; Carlson & Jorgensen, 1995] offer detail on the distinct nature of water around the solute and are transferable across a wide range of data sets, although there is a lack of throughput in the field of drug design.
Implicit solvation models offer a faster alternative to explicit models by replacing the individual water molecules with a continuous medium [Baker, 2005; Chen et al., 2008], combining the hydration free energy density and group contribution [Jäger & Kast, 2001], or, more recently, calculating solvation free energy directly from the molecular structure [Delgado & Jaña, 2009]. For small organic molecules, the loss of molecular detail of the solvent results in relatively small differences between hydration free energy prediction accuracies calculated with explicit solvent models relative to the explicit treatment [Mobley et al., 2009; Nicholls et al., 2009]. To cope with some of these pitfalls, the variational implicit solvent model (VISM) has been proposed for calculating the solute/water interface where established models fail [Dzubiella et al., 2006a, 2006b].
It is sometimes possible to get quite accurate results with very simple models, such as the case of the molecular modellisation of phenethylamine carriers conducted in our lab. Calculations were carried out using chloride anion to mimic the picrate anion used in experimental measurements and with no explicit solvent molecules. The chloroform environment was simulated by a constant dielectric factor, as this solvent has a low dielectric constant and thus, interactions should not end quickly with the distance [Campayo et al., 2005]. When complexation takes place in water as the solvent, the environment is simulated by a distance-dependent dielectric factor, as it takes into account the fact that the intermolecular electrostatic interactions should vanish with distance faster than in the gas phase. This assumption proves to work as it gives theoretical results in good agreement with experimental transportation values [Miranda et al., 2004; Reviriego et al., 2008]. Results for theoretical interactions have been supported by NMR experiments.
When applied to complex biomolecular systems, this loss of detail may become problematic in locations where water does not behave as a continuum medium, for example, the individual water molecules occurring in concave pockets at the surfaces of proteins [Li & Lazaridis, 2007]. The ELSCA (Energy by Linear Superposition of Corrections Approximation) method [Cerutti et al., 2005] has also been proposed for the rapid estimation of solvation energies. This procedure calculates the electrostatic and apolar solvation energy of bringing two proteins into close proximity or into contact compatible with the AMBER ff99 parameter set. The method is most useful in macromolecular docking and protein association simulations.
Solvent treatment is also of considerable interest in MD simulations as the solvent molecules (usually water, sometimes co-solvent and counterions/buffer or salt for electrolyte solutions) enter pockets and inner cavities of the proteins through their conformational changes. This is a very slow process and nearly as difficult to model as protein solving. One solution to this problem is using an efficient coupling of molecular dynamics simulation with the 3D molecular theory of solvation (3D-RISM-KH), contracting the solvent degrees of freedom [Luchko et al., 2010] or using free energy perturbation and OPLS force field together with molecular dynamics [Shivakumer et al., 2010].
4. Molecule-molecule or ion-molecule interactions in active molecule design
Non-covalent interactions are central to biological structure and function. In considering potential interactions of molecules and/or ions and their receptor, the focus has been on hydrophobic interactions, hydrogen bonding and ion pairing. Although hydrogen bonds are by far the most important interactions in biological recognition processes, the cation-π interaction is a general, strong, non-covalent binding force that occurs throughout nature, being energetically comparable or stronger than a typical hydrogen bond.
Cooperativity in multiple weak bonds (hydrogen bond and ion-π interactions among others) has been considered and studied at the MP2/6-311++ G(d,p) computational level [Alkorta et al., 2010]. Due to the presence of a great number of aromatic rings containing heteroatoms in biological systems, this effect might be important and help to understand some biological processes where the interplay between both interactions may exist.
Computer-assisted drug design (CADD) has contributed to the successful discovery of numerous novel enzyme inhibitors, having been used to predict the binding affinity of an inhibitor designed from a lead compound prior to synthesis [Reddy & Erion, 2005]. A free energy simulation technique known as the thermodynamic cycle perturbation (TCP) approach [Reddy et al., 2007], used together with calculations of molecular dynamics, offers a theoretically precise method to determine the binding free energy differences of related inhibitors.
Many small molecules are transported across cell membranes by large integral membrane proteins, which are referred generically as transporters. Selection among competing alternatives is always interesting and cation-π interactions are strongly involved in substrate recognition by many transporters. Drug transporters are able to carry small molecules or ions across membranes, being an important target for pharmaceutical development [Zacharias & Dougherty, 2002].
The regulation of metal ions plays a major role in enzymes, allowing to catalyse a range of biological reactions. Identification and characterisation of the metal ion binding sites and their selectivity have received immense attention over the past few decades [Ma & Dougherty, 1997]. It is evident from earlier studies that metal ions can bind to aromatic groups in a covalent as well as non-covalent fashion. Non-covalent interactions between metal ions and an aromatic ring, which are considered strong cation-aromatic interactions, are increasingly being recognised as an important binding force relevant to structural biology [Meyar et al., 2003; Elguero et al., 2009]. However, in many cases, the cation is the side chain protonated nitrogen of a basic amino acid. Reddy et al. have made available a web-based cation-aromatic database (CAD) including metal ions and basic amino acids [Reddy et al., 2007b].
Macrocyclic entities that act as ion receptors and carriers exhibit a large number of conformations in crystals and solutions, depending on the nature of their environments and of the complexed ion. To ensure the formation of the most favourable cavity for a given ion, as well as to enhance the binding and release of the ion during transport at interfaces, flexibility in the ligand structure is of utmost importance.
Complexation studies of ions with macrocycles are well documented in the literature. Some representative trends in these studies would include the following: taking into account the existence of hydrogen-bonded water molecules [Hill & Feller, 2000; Durand et al., 2000; Fantoni, 2003] and sometimes using molecular dynamics and free energy perturbation studies [Varnek et al., 1999]. The complexation phenomena have also been studied in cases where the ligand can exist as different conformers able to complex the cation [Hashimoto & Ikuta, 1999].
One of the most important aspects of ion complexation is ion selectivity, which is considered in terms of the more or less favourable binding energies. The binding energy (BE) is defined as the difference between the energy of the complex and the energy of the free ligand and ion:
BE = Ecomplex – (Eion + Eligand)
Metal ion affinity is enhanced if the host molecule has a unique conformation that is optimal for complexation, that is, with all the binding sites positioned to structurally complement the metal ion [Lumetta et al., 2002].
Density functional theory based on electronic structure calculations is computationally affordable. It has very good predictability power for various structural and thermodynamic properties of a molecular system, and has therefore been used to model M+-crown ether complexes [Ali et al., 2008] and collarenes acting as ionophores and receptors [Choi et al., 1998]. In both cases, the most stable equilibrium structure for complexes are estimated based on PM3 semi-empirical calculations followed by B3LYP calculations using the G-311++G(d,p) basis set of functions. Currently, the Protein Data Bank (PDB) contains over 25,000 structures that contain a metal ion. Thus, methodologies to incorporate metal ions into the AMBER force field have been developed there [Hoops et al., 1991; Reichert et al., 2001; Peters et al., 2010].
Molecular modellisation of Cu(II) and Zn(II) coordination complexes has been studied by our research group, among many others. The parameters used by us were checked against a known X-ray structure and the data obtained agreed quite well with similar deviations published for other theoretical results [Miranda et al., 2005]. The models obtained were useful in explaining the differences observed among the complexes obtained in different environments. Our cation metal parameters have also been used to help in the data elucidation of coordination metal complex structures [Rodríguez-Ciria, 2000; Rodríguez-Ciria et al., 2002].
Coordination and complexation of ions by aromatic moieties have been studied, taking into account the different characteristics of the electronic charge distribution on the aromatic frame as an addition of coulombic potentials [Albertí et al., 2010]. This type of interaction is quite common in biology as signalling in the nervous system is generally mediated by the binding of small molecules (neurotransmitters) to the appropriate receptors, which usually contain a cationic group at physiological pH.
An organic ammonium ion never exists as a sole cation; an anion is always associated with it. Depending on the polarity and hydrogen donor/acceptor abilities of the solvent, the association strength is different [Marcus & Hefter, 2006]. Strongly coordinating counter ions such as chloride generally lead to weaker binding constants upon recognition of the associated cation, when compared to weakly coordinating counterions such as iodide or perchlorate [Gevorkyan et al., 2001].
5. Selective formation of complexes
There are several examples of molecular modelling studies on complexes between cyclic receptors and ammonium ions, calixarenes [Choe & Chang, 2002] and crown ethers being the most used. As an example, it is noteworthy to mention the theoretical studies on calix[4]crown-5 and a series of alkyl ammonium ions [Park et al., 2007], having shown that the energy of complex formation depends on the number of amine groups in the alkyl chain as well as on the number of methylene groups between the primary and secondary amine groups, results that agree with experimental measurements. Although the calculations are performed under quite different conditions of vacuum compared with the experimental conditions of the phase system of chloroform-water, the binding properties of calixarene-type compounds towards alkyl ammonium ions have been successfully simulated, providing general and useful explanations for the molecular recognition behaviour.
Complex formation of compounds containing benzene rings with ammonium cations has also been theoretically studied using many computational techniques, including ab initio calculations [Kim et al., 2000]. It has been shown that two types of NH-aromatic π and CH-aromatic π interactions, which are important in biological systems, are responsible for binding, and that charged hydrogen bonds versus cation-π interaction is the origin of the high affinity and selectivity of novel receptors for NH4+ over K+ ions [Oh et al., 2000]. Organic molecules complexed with metal cations have also been studied by MM2 molecular modelling [Mishra, 2010]. The search for metal ion selectivity is of interest in the field of biomimetic models of metalloenzymes and molecular modelling helps in the design of new ligands with this purpose [Kaye, 2011].
Molecular modelling has been used to suggest possible contributions of carrier effectivity and selectivity to complex formation in accordance with experimental results [Chipot et al., 1996; Ilioudis et al., 2005]. Our research group has evaluated the possible cation-receptor interactions involved in the complexes with ammonium and metal cations of selective carriers using the Amber force field with appropriate parameters developed by us. The complexation energies obtained are in reasonable agreement with experimental values, taking into account that complexation/decomplexation processes have a great influence on transport rates and are not equally favoured in cyclic and acyclic carriers [Campayo et al., 2004].
Both binding and selectivity in binding can be understood through the combined efforts of several non-covalent interactions, such as hydrogen bonding, electrostatic interactions, hydrophobic interactions, cation-π interactions, π-π stacking interactions and steric complementarity [Späth & König, 2010]. Formation of complexes is also possible in the case of neutral ligands. For example, the interactions between cholesterol and cyclodextrins have been theoretically studied to investigate their 1:1 and 1:2 complexes [Castagne et al., 2010], while the formation of stable complexes between trehalose and benzene compounds have been investigated by the general Amber force field (GAFF) and Gaussian 03 for MP2/6G-31G** calculation of atomic charges [Sakakura et al., 2011].
Docking of a ligand into a receptor may occur via an automated procedure [Subramanian et al., 2000] or manually [Filizola et al., 1999]. In both cases, docking is a combination of two components: a search strategy and a scoring function [Taylor et al., 2002]. The computational method MOLINE (Molecular Interaction Evaluation) was created to study complexes in an unbiased fashion [Alcaro et al., 2000]. It is based on a systematic, automatic and quasi-flexible docking approach that prevents the influence of the chemist`s intuition on generating the configuration. This method has been used with acceptable results in studying inclusion complexes [Alcaro et al., 2004].
It would be adequate at this point to remember that testing the `drug-receptor complexation’ for a receptor model against available experimental data usually involves the use of site-directed mutagenesis experiments. This fact provides information on the amino acids involved in ligand binding and receptor activation. However, it should be noted that the results of mutagenesis studies are not necessarily related to receptor-ligand interactions. In fact, mutations can also alter the 3D structure of a receptor and therefore, modify the binding profile of a ligand by this mechanism. Besides that, efficient binding to a receptor does not guarantee that a ligand will produce a pharmacological action, given that the ligand may act as an agonist or antagonist.
6. Interaction of molecules with DNA
Anthracycline antibiotics such as doxorubicin and its analogues have been in common use as anticancer drugs for around half a century. There has been intense interest in the DNA-binding sequence specificity of these compounds in recent years, with the hope of identifying a compound that can modulate gene expression or exhibit reduced toxicity. Cashman and Kellog have studied models of binding for doxorubicin and derivatives [Cashman & Kellog, 2004], looking for sequence specificity and the effects of adding aromatic or aliphatic ring substituents or additional amino or hydroxyl groups. They performed a hydropathic interaction analysis using the HINT program (a Sybyl program module, Tripos Inc.) and four double base pair combinations. Interaction of some intercalators with two double DNA base pairs have also been studied with the density functional based tight binding (DFTB) method [Riahi et al., 2010], despite DFT methods being known to be inherently deficient in calculating stacking interactions, and the Amber force field and then AM1 to dock the intercalator between DNA base pairs [Miri et al., 2004].
Studies on sequence-selectivity of DNA minor groove binding ligands have shown that the most reliable results for AT-rich DNA sequences are obtained when MD simulations are performed in explicit solvent, when the data are processed using the MM-PB/SA approach, and when normal mode analysis is used to estimate configurational entropy changes [Shaikh et al., 2004; Wang & Laughton, 2009]. Use of the GB/SE model with a suitable choice of parameters adequately reproduces the structural and dynamic characteristics in explicitly solvated simulations in approximately a quarter of the computational time, although limitations become apparent when the thermodynamic properties are evaluated [Sands & Laughton, 2004]. Water molecules taking part in the complexation have been studied using the MMX force field and then PMB for gas phase optimisation, followed by re-optimisation in aqueous phase with the PM3 method using the AMSOL package [Silva & Jayasundera, 2002]. Optimisation geometries with AM1 and the use of implicit solvent have been taken into account when considering intercalation versus insertion into the minor or major groove [Bendic & Volanschi, 2006].
Calculating the curvature radius of molecular DNA structures has been reported [Slickers et al., 1998] as a new method for understanding the dependence of binding affinity on ligand structure, assuming that strong binders should have a shape complementary to the DNA minor groove. A method for predicting sequence selectivity and minor groove binding, based on MD simulations on DNA sequences with and without the bound ligand, to obtain an approximate free energy of binding has been proposed [Wang & Laughton, 2010].
Amber force field, developing the necessary parameters, has also been used together with electrostatic potential-derived (ESP) charges and explicit solvent molecules to study bisintercalation into DNA. The targeted molecular dynamics (tMD) approach has been considered for comparing the relative energetic cost involved in creating the intercalation sites and also studying the mechanisms of action [Braña et al., 2004]. It has been found that the electrostatic contribution is a critical characteristic of binding selectivity [Marco et al., 2005]. Reports on duplex and triplex formation of oligonucleotides by stacking aromatic moieties in the major groove, using Amber force field and the GB/SA solvation model in molecular dynamic simulations, can be found in the literature [Andersen et al., 2011]. Studies on docking using GOLD [Kiselev et al., 2010] to optimise the starting structures with the MMFF94 force field have also been performed.
Most of the published molecular modelling studies use two double base pairs or more than eight double base pairs to represent DNA. In our opinion, molecular modelling of DNA intercalation complexes should be done using at least the two base pairs of the intercalation site and an additional base pair at the two strand ends to maintain DNA shape and avoid distortion leading to inaccurate results. That means four base pairs for monointercalation studies and five or six base pairs for bisintercalation ones should be used. Using these DNA models, our studies on the mono and bisintercalation of benzo[g]phthalazine derivatives strongly suggest the possibility of bisintercalation and the important role played by an N-methyl group in stabilising the DNA complex of one of the compounds, throwing some light over the experimental results obtained [Rodríguez-Ciria et al., 2003]. The possibility of bisintercalation for a 1,4-disubstituted piperazine has been studied on duplexes of five and six base pairs, obtaining much better results in the case of five base pairs, in accordance with the theoretical calculations of binding mode not conforming to the neighbouring exclusion principle proposed by different authors [Veal et al., 1990].
7. Interaction of small molecules with enzymes
The potential of molecular simulations to enhance our understanding of drug behaviour and resistance relies ultimately on their ability to achieve an accurate ranking of drug binding affinities at clinically relevant time scales. Several computational approaches exist to estimate ligand binding affinities and selectivities, with various levels of accuracy and computational expense: free energy perturbation (FEP), thermodynamic integration (TI), lineal response (LR), and molecular mechanics Poisson-Boltzman surface area (MM/PBSA). Identification of conformational preferences and binding site residues, as well as structural and energetic characterisation, is possible using MD simulations [Anzini et al., 2011; Dastidor et al., 2008; Stoika et al., 2008]. It is also possible to estimate conformational energy penalties for adopting the bioactive conformation identified by using a pharmacophore model [Frølund et al., 2005].
A model based on van der Waals intermolecular contribution from Amber and electrostatic interactions derived from the Poisson-Boltzman equation has been used to predict the change in the apparent dissociation constant for a series of six enzyme-substrate complexes during COMBINE analysis [Kmunicek et al., 2001]. In COMBINE analysis, binding energies are calculated for the set of enzyme-substrate complexes using the molecular mechanics force field. The total binding energy, ΔU, may be assumed to be the sum of five terms: the intermolecular interaction energies between the substrate and each enzyme residue, EinterES, the change in the intramolecular energy of the substrate upon binding to the enzyme, ΔES, the change in the intramolecular energy of the enzyme upon binding, ΔEE, the desolvation energy of the substrate, EdesolvS, and the desolvation energy of the enzyme, EdesolvE.
ΔU = EinterES + ΔES + ΔEE + EdesolvS + EdesolvE
When the substrate is a rather small molecule, there is no evidence for large differences in the structure of the enzyme when different substrates are bound and so the second and third are neglected. This method identifies the amino acid residues responsible for modulating enzyme activity [Kmunicek et al., 2005].
Molecular modelling of proteins is sometimes directed towards homology modelling, enabling progress in understanding the mechanisms of action despite the lack of detailed information on the 3D structure of a protein. Molecular dynamic simulations are usually used to test the stability of the complete structure derived from homology modelling [Srinivas et al., 2006].
Molecular docking examples can be used to compare relative stabilities of the complexes, but not calculate binding affinities, since changes in entropy and solvation effects are not taken into account [Pastorin et al., 2006; Tschammer et al., 2011]. In any case, docking calculations are common studies on novel drugs, Autodock being one of the most used docking programs [see for example Venskutonyte et al., 2011]. Docking programs treat enzymes and substrates as rigid entities, but flexible docking is also possible, if several different protein conformations extracted from molecular dynamic simulations are used [Roumen et al., 2010].
In our laboratory, molecular modelling has been tentatively used to study the trypanosomicidal activity of some phthalazine derivatives. Results obtained with Amber force field implemented in HyperChem 8.0 plus our own necessary parameters, and with AutoDock 4.2 using the PDB structure for T. cruzi Fe-SOD enzyme, were in accordance with experimental data, helping to explain the experimental results obtained. However, if there is no PDB structure for the desired enzyme and only a model of the active site, as for Leishmania Fe-SOD enzyme, results obtained with our calculations do not agree with the experimental ones when compared to the T. cruzi ones. This indicates that the interaction with the external part of the enzyme plays an important role as it might collaborate in, or make access to the active site difficult, since the enzyme shape and conformation plays a crucial role in its activity [Sanchez-Moreno et al., 2011; Yunta, unpublished results].
8. Conclusion
Modern molecular modelling techniques are remarkable tools in the search for potentially novel active agents by helping to understand and predict the behaviour of molecular systems, having assumed an important role in the development and optimisation of leading compounds. Moreover, current information on the 3D structure of proteins and their functions provide a possibility of understanding the relevant molecular interactions between a ligand and a target macromolecule. Although improvements are still needed in the techniques used, they have been shown to be invaluable in structure–activity relationship research.
On the basis of the current improved level of understanding of molecular recognition and the widespread availability of target structures, it is reasonable to assume that computational methods will continue to aid not only the design and interpretation of hypothesis-driven experiments in disease research, but also the fast generation of new hypotheses.
Acknowledgement
Financial support from the Spanish MEC project (CGL2008-0367-E/BOS) and the MCINN projects (CTQ2009-14288-C04-01 and CONSOLIDER INGENIO 2010 CSD2010-00065) are gratefully acknowledged.
\n',keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/41239.pdf",chapterXML:"https://mts.intechopen.com/source/xml/41239.xml",downloadPdfUrl:"/chapter/pdf-download/41239",previewPdfUrl:"/chapter/pdf-preview/41239",totalDownloads:3698,totalViews:536,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,dateSubmitted:"May 19th 2011",dateReviewed:"October 2nd 2012",datePrePublished:null,datePublished:"November 28th 2012",dateFinished:null,readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/41239",risUrl:"/chapter/ris/41239",book:{slug:"bioinformatics"},signatures:"María J. R. Yunta",authors:[{id:"107394",title:"Dr.",name:"Maria",middleName:"Josefa Rodriguez",surname:"Yunta",fullName:"Maria Yunta",slug:"maria-yunta",email:"mjryun@quim.ucm.es",position:null,institution:{name:"Complutense University of Madrid",institutionURL:null,country:{name:"Spain"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Molecular modelling methods and their usefulness",level:"1"},{id:"sec_2_2",title:"2.1. Molecular mechanics, molecular dynamics and docking",level:"2"},{id:"sec_3_2",title:"2.2. Most used existing force fields",level:"2"},{id:"sec_4_2",title:"2.3. Popular docking programs",level:"2"},{id:"sec_6",title:"3. The solvent and how to model it",level:"1"},{id:"sec_7",title:"4. Molecule-molecule or ion-molecule interactions in active molecule design",level:"1"},{id:"sec_8",title:"5. Selective formation of complexes",level:"1"},{id:"sec_9",title:"6. Interaction of molecules with DNA",level:"1"},{id:"sec_10",title:"7. Interaction of small molecules with enzymes",level:"1"},{id:"sec_11",title:"8. Conclusion",level:"1"},{id:"sec_11_2",title:"Acknowledgement",level:"2"}],chapterReferences:[{id:"B1",body:'AjayMurcko, M.A. (1995Computational methods to predict binding free energy in ligand-receptor complexes.J. Med. Chem., 3826December 1995), 495349670022-2623'},{id:"B2",body:'AlbertíMAguilarALucasJ. MPiraniF2010A generalized formulation of ion-π electron interactions: role of the nonelectrostatic component and probe of the potential parameter transferability. J. Phys. Chem. A, 11444November 2010), 11964119701089-5639'},{id:"B3",body:'AlcaroSBattagliaDOrtusoF2004Molecular modeling of β-cyclodextrin inclusions complexes with pharmaceutical compounds. Arkivoc, 20045February 2004), 1071171424-6376'},{id:"B4",body:'AlcaroSGasparriniFIncaniOMecucciSMisitiDPieriniMVillaniC2000AQuasi-flexibleautomatic docking processing for sudying stereoselective recognition mechanisms. Part 1. Protocol validation. J. Comput. Chem., 217May 2000), 5155300109-6987X'},{id:"B5",body:'AliSk.M., Mainly, D.K., De, S. & Shenoi, M.R.K. (2008Ligands for selective metal ion extraction: a molecular modeling approachDesalination2321-3November 2008), 1811900011-9164'},{id:"B6",body:'AlkortaIBlancoFDeyaP. MElgueroJEstarellasCFronteraAQuinoneroD2010Cooperativity in multiple unusual weak bonds. Theor. Chem. Acc., 1261-2May 2010), 1141432-2234'},{id:"B7",body:'AllingerN. L1976Calculation of molecular structure and energy by force field methods, In: Advances in Physical Organic Chemistry, 13Gold, V & Bethell, D. (Eds.), 182Elsevier, 978-0-12033-513-8Amsterdam'},{id:"B8",body:'AllingerN. LChenKLiiJ. H1996An improved force field (MM4) for saturated hydrocarbonsJ. Comput. Chem., 175-6April 1996), 6426680109-6987X'},{id:"B9",body:'AllingerN. LDurkinK. A2000Van der Waals effects between hydrogen and first row atoms in molecular mechanics (MM3/MM4)J. Comput. Chem., 2114November 2000), 122912420109-6987X'},{id:"B10",body:'AllingerN. LYanQ. L1993Molecular mechanics (MM3)- calculations of vinyl ethers, and related compounds. J. Am. Chem. Soc., 115199311918119250002-7863'},{id:"B11",body:'AndersenN. KDossingHJensenFVesterBNielsenP2011Duplex and triplex formation of mixed pyrimidine oligonucleotides with stacking of phenyl-triazole moieties in the major groove. J. Org. Chem., 7615August 2011), 617761870022-3263'},{id:"B12",body:'AnziniMValentiSBraileCCappelliAVomeroSAlcaroSOrtusoFMarinelliLLimongelliVNovellinoEBettiLGiannacciniGLucacchiniADanieleSMartiniCGhelardiniCMannelliL. D. CGiorgiGMasciaM. PBiggioG2011New insight into the central benzodiazepine receptor-ligand interactions: design, synthesis, biological evaluation, and molecular modeling of 3-substituted 6-phenyl-4H-imidazo[1,5-a][1,4]benzodiazepines and related compounds. JMed. Chem., 5416August 2011), 569457110022-2623'},{id:"B13",body:'AqvistJMedinaCSamuelsonJ. E1994A new method for predicting binding affinity in computer aided drug design.Protein Eng. 73March 1994), 3853910269-2139'},{id:"B14",body:'BakerN. A2005Improving implicit solvent simulations: a poisson-centric viewCurr. Opin. Struct. Biol., 152April 2005), 1371430095-9440X'},{id:"B15",body:'BendicCVolanschiE2006Molecular modeling of the interaction of some phenoxazone-antitumoral drugs with DNA. Int. Elect. J. Mol. Des., 56June 2006), 3203301538-6414'},{id:"B16",body:'BissantzCKuhnBStahlM2010A medicinal chemist’s guide to molecular interactionsJ. Med. Chem, 5314July 2010), 506150840022-2623'},{id:"B17",body:'BranaM. FCachoMGarcíaM. APascual-teresaBRamosADominguezM. TPozueloJ. MAbradeloCRey-stolleM. FYusteMBanez-coronelMLacalJ. C2004New analogues of amonafide and elinafide, containing aromatic heterocycles: synthesis, antitumor activity, molecular modeling, and DNA binding properties. J. Med. Chem., 476March 2004), 139113990022-2623'},{id:"B18",body:'BrooksB. RBruccoleriR. EOlafsonB. DStalesD. JSwaminathanSKarplusM1983CHARMM: A program for macromolecular energy, minimization and dynamic calculations.J. Comput. Chem., 42July 1983), 1872170109-6987X'},{id:"B19",body:'BuchISadigS. KDefabritiisG2011Optimized potential of mean force calculations for standard binding free energiesJ. Chem. Theory Comp., 76June 2011), 176517721549-9626'},{id:"B20",body:'CampayoLCalzadoFCanoM. CYuntaM. J. RPardoMNavarroPJimenoM. LGómez-contrerasFSanzA. M2005New acyclic receptors containing pyridazine units. The influence of π-stacking on the selective transport of lipophilic phenethylamines. Tetrahedron, 6150December 2005), 11965119750040-4020'},{id:"B21",body:'CampayoLPardoMCotillasAJaúreguiOYuntaM. J. RCanoMGómez-contrerasFNavarroPSanzA. M2004A new series of heteroaromatic receptors containing the 1,3-bis(6-oxopyridazin-1-yl)propane unit: their selective transport ability towards NH4+ in relation to Na+, K+ and Ca2+Tetrahedron604January 2004), 9799860040-4020'},{id:"B22",body:'CarlsonH. AJorgensenW. L1995An extended linear response method for determining free energies of hydrationJ. Phys. Chem., 9926June 1995), 10667106730022-3654'},{id:"B23",body:'CashmanD. JKelloggG. E2004A computational model for anthracycline binding to DNA: Tuning groove-binding intercalators for specific sequences.J. Med. Chem., 476March 2004), 136013740022-2623'},{id:"B24",body:'CastagneDDiveGEvradBFrédérichMPielG2010Spectroscopic studies and molecular modeling for understanding the interactions between cholesterol and cyclodextrinsJ. Pharm. Pharmaceut. Sci., 133July 2010), 3623671482-1826'},{id:"B25",body:'ČernýV1985Thermodynamical approach to the traveling salesman problem: An efficient simulation algorithm. J. Optimization Theory and Applications, 451January 1985): 41510022-3239'},{id:"B26",body:'CeruttiD. STen Eyck, L.F. & McCammon, J.A. (2005Rapid estimation of solvation energy for simulations of protein-protein association. J. Chem. Theory Comput., 11January 2005), 1431521549-9626'},{id:"B27",body:'ChambersC. CHawkinsG. DCramerC. JTruhlarD. G1996Model for aqueous solvation based on class IV atomic charges and first solvation shell effectsJ. Phys. Chem., 10040October 1996), 16385163980022-3654'},{id:"B28",body:'ChecaAOrtizA. RPascual-teresaBGagoF1997Assessment of solvation effects on calculated binding affinity differences: Trypsin inhibition by flavonoids as a model system for congeneric seriesJ. Med. Chem., 4025December 1997), 413641450022-2623'},{id:"B29",body:'ChenJBrooksC. LIII & Khandogin, J. (2008Recent advances in implicit solvent-based methods for biomolecular simulationsCurr. Opin. Struct. Biol., 182April 2008), 1401480095-9440X'},{id:"B30",body:'ChipotCMaigretBPearlmanD. AKollmanP. A1996Molecular dynamics potential of mean force calculations: a study of the toluene-ammonium π-cation interactions. J. Am. Chem. Soc., 11812March 1996), 299830050002-7863'},{id:"B31",body:'ChoeJ. IChangS. K2002Molecular modeling of complexation behavior of p-tert-butylcalix[5]arene derivative toward butylammonium ions. Bull. Korean Chem. Soc., 231January 2002), 48520253-2964'},{id:"B32",body:'ChoiH. SSuhS. BChoS. JKimK. S1998Ionophores and receptors using cation-π interactions: collarenes. Proc. Natl. Acad. Sci. USA, 9521October 1998), 1209412099ISNN: 1091-6490'},{id:"B33",body:'CornellW. DCieplakPBaylyC. IGouldI. RMerzK. MJr., Ferguson, D.M., Spellmeyer, D.C., Fox, T., Caldwell, J.W. & Kollman, P.A. (1995A second generation force field for thr simulation of proteins and nucleic acids. J. Am. Chem. Soc., 11719May 1995), 517951970002-7863'},{id:"B34",body:'CramerC. JTruhlarD. G2008A universal approach to solvation modeling.Acc. Chem. Res., 416June 2008), 7607680001-4842'},{id:"B35",body:'CramerR. DPattersonD. EBunceJ. D1988Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins. J. Am. Chem. Soc., 11018August 1998), 595959670002-7863'},{id:"B36",body:'CruzianiGGoodfordP. J1994A research for specificity in DNA-drug interactions. J. Mol. Graph., 122June 1994), 1161290263-7855'},{id:"B37",body:'DastiderS. GLaneD. PVermaC. S2008Multiple peptide conformations give rise to similar binding affinities: molecular simulations of p53-MDM2. J. Am. Chem. Soc., 13041October 2008), 13514135150002-7863'},{id:"B38",body:'Dauber-osguthorpePRobertsV. AOsguthorpeD. JWolffJGenestMHaglerA. T2004Structure and energetics of ligand binding to proteins: E. coli dihydrofolate reductase- trimethoprim, a drug-receptor system. Proteins, 41February 2004), 31470887-3585'},{id:"B39",body:'DelgadoE. JJanaG. A2009Quantitative prediction of solvation free energy in octanol of organic compounds. Int. J. Mol. Sci., 103March 2009), 103110441422-0067'},{id:"B40",body:'DoshiUHamelbergD2009Reoptimization of the AMBER force field parameters for peptide bond (omega) torsions using accelerated molecular dynamicsJ. Phys. Chem. B, 11352December 2009), 16590165951089-5647'},{id:"B41",body:'DurandSDognonJ. PGuibandPRabbeCWipffG2000Lanthanide and alkaline-earth complexes of EDTA in water: a molecular dynamics study of structures and binding selectivitiesJ. Chem. Soc., Perkin Trans. 2, 20004April 2000), 7057141364-5471\n\t\t\t'},{id:"B42",body:'DzubiellaJSwansonJ. M. JMccammonJ. A2006aCoupling nonpolar and polar solvation free energies in implicit solvent models.J. Chem. Phys., 124February 2006), 0849050021-9606'},{id:"B43",body:'DzubiellaJSwansonJ. M. JMccammonJ. A2006bCoupling hydrophobicity dispersion, and electrostatics in continuum solvent models.Phys. Rev. Lett., 968March 2006), 0878021079-7114'},{id:"B44",body:'ElberRRotbergASimmerlingCGoldsteinRLiHVerkhivkerGKeasarCZhangJUlitskyA1995MOIL: A program for simulations of macromoleculesComp. Phys. Comm., 911-3September 1995), 1591891815-2406'},{id:"B45",body:'ElgueroJAlkortaIClaramuntR. MLópezCSanzDSanta María, D. (2009Theoretical calculations of a model of NOS indazole inhibitors: Interaction of aromatic compounds with Zn-porphyrinsBioorg. Med. Chem., 1723December 2009), 802780310968-0896'},{id:"B46",body:'FantoniA. C2003Molecular dynamics study of geometrical isomers of a pyridinocalix[4]arene in methanol solution: solvation and alkali metal cation binding propertiesJ. Mol. Struct. (Theochem), 6931August 2003), 160166-1280'},{id:"B47",body:'FilizolaMCarteri-farinaMPerezJ. J1999Molecular modeling study of the differential ligand-receptor interaction at the μ, δ and κ opioid receptors. J. Comput. Aid. Mol. Des., 134July 1999), 3974071573-4951'},{id:"B48",body:'FriesnerR. ABanksJ. LMurphyR. BHalgrenT. AKlicicJ. JMainzD. TRepaskyM. PKnollE. HShelleyMPerryJ. KShawD. EFrancisPShenkinP. S2004Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracyJ. Med. Chem., 477March 2004), 173917490022-2623'},{id:"B49",body:'FriesnerR. AMurphyR. BRepaskyM. PFryeL. LGreenwoodJ. RHalgrenT. ASanschagrinP. CMainzD. T2006Extra precision Glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes.J. Med. Chem., 4921October 2006), 617761960022-2623'},{id:"B50",body:'FrolundBJensenL. SGuandaliniLCanilloCVestergarardH. TKristiansenUNielsenBStensbolT. BMadsenCKrogsgaard-larsenPLiljeforsT2005Potent 4-aryl- or 4-arylalkyl-substituted 3-isoxazolol GABAA antagonists: synthesis, pharmacology, and molecular modeling. J. Med. Chem., 482January 2005), 4274390022-2623'},{id:"B51",body:'GalisteoJNavarroPCampayoLYuntaM. J. RGómez-contrerasFVilla-pulgarinJ. ASierraB. GMollinedoFGonzalezJGarcía-espanaE2010Synthesis and cytotoxic activity of a new potential bisintercalator: 1,4-bis{3-[N-(4-chlorobenzo[g]phthalazin-1-yl)aminopropil]}piperazine. Bioorg. Med. Chem., 1814July 2010), 530153090968-0896'},{id:"B52",body:'GallicchioELevyR. M2004AGBNP: An analytical implicit solvent model suitable for molecular dynamics simulations and high-resolution modeling. J. Comput. Chem., 254March 2004), 4794990109-6987X'},{id:"B53",body:'GallicchioEZhangL. YLevyR. M2002The SGB/NP hydration free energy model based on the surface generalized born solvent reaction field and novel nonpolar hydration free energy estimators.J. Comput. Chem., 235April 2002), 5175290109-6987X'},{id:"B54",body:'GevorkyanA. AArakelyanA. SEsayanV. APetrosyanK. ATorosyanG. O2001Ionic character of the ammonium-counterion bond and catalytic activity of ammonium salts in elimination reactionsGen. Chem., 718August 2001), 132713281070-3632'},{id:"B55",body:'GilsonM. KZhouH. X2007Calculation of protein-ligand binding affinities.Annu. Rev. Biophys. Biomol. Struct., 36June 2007), 21421056-8700'},{id:"B56",body:'GoodfordP. J1985A computational procedure for determining energetically favorable binding sites on biologically important macromolecules.J. Med. Chem., 188August 1985), 8498570022-2623'},{id:"B57",body:'HalgrenT. A1996Merck molecular force field. 1. Basis, form, scope, parameterización, and performanceof MMFF9J. Comput. Chem., 175-6April 1996), 4905190109-6987X'},{id:"B58",body:'HalgrenT. AMurphyR. BFriesnerR. ABeardH. SFrieL. LPollardW. TBanksJ. L2004Glide: A new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening.J. Med. Chem., 477March 2004), 175017590022-2623'},{id:"B59",body:'HashimotoSIkutaS1999A theoretical study on the conformations, energetics, and solvation effects on the cation-π interaction between monovalent ions Li+, Na+ and K+ and naphthalene molecules. J. Mol. Struct. (Theochem), 4681-2August 1999), 85940166-1280'},{id:"B60",body:'HillS. EFellerD2000Theoretical study of cation/ether complexes: 15-crown-5 and its alkali metal complexesInt. J. of Mass Spect., 2011-3December 2000), 41581387-3806'},{id:"B61",body:'HoopsS. CAndersonK. WMerzK. MJr. (1991Force field design for metalloproteinsJ. Am. Chem. Soc., 11322October 1991), 826282700002-7863'},{id:"B62",body:'HortaB. A. CFuchsP. F. JVan GunsterenW. FHunenbergerP. H2011New interaction parameters for oxygen compounds in the GROMOS force field: improved pure-liquid and solvation properties for alcohols, ethers, aldehydes, ketones, carboxylic acids and esters.J. Chem. Theory Comp., 74April 2011), 101610311549-9626'},{id:"B63",body:'IlioudisC. ABearparkM. JSteadJ. W2005Hydrogen bonds between ammonium ions and aromatic rings exist and have key consequences on solid-state and solution phase propertiesNew J. Chem., 291January 2005), 64671144-0546'},{id:"B64",body:'JagerRKastS. M2001Fast prediction of hydration free energies from molecular interaction fields.J. Mol. Graphs. Mod., 201February 2001), 1231311093-3263'},{id:"B65",body:'JainA. N2003Surflex: Fully automatic flexible molecular docking using a molecular similarity-based search engine.J. Med. Chem., 464February 2003), 4995110022-2623'},{id:"B66",body:'JainA. N2007Surflex-Dock 2.1: Robust performance from ligand energetic modeling, ring flexibility, and knowledge-based searchJ. Comput. Aid. Mol. Des., 215May 2007), 2813061573-4951'},{id:"B67",body:'JorgensenW. LTirado-rivesJ1996Monte Carlo vs molecular dynamics for conformational samplingJ. Phys. Chem., 10034August 1996), 14508145130022-3654'},{id:"B68",body:'KayeP. T2011Designer ligands: The search for the metal ion selectivity. S. Afr. J. Sci., 1073-4March 2011), 4394460038-2353'},{id:"B69",body:'KhavretskiiI. VWallquistA2010Computing relative energies of solvation using single reference thermodynamic integration augmented with Hamiltonian replica exchange. J. Chem. Theor. Comput., 611342734411549-9626'},{id:"B70",body:'KimK. SLeeJ. YTarakeshwarP2000Molecular clusters of π-systems: Theoretical studies of structures, spectra, and origin of interaction energies. Chem. Rev., 10011November, 2000), 414541860009-2665'},{id:"B71",body:'KirkpatrickSGelattC. DVecchiM. P1983Optimization by Simulated AnnealingScience, 2204598May 1983) 6716800036-8075'},{id:"B72",body:'KiselevEDexheimerTPommierYCushmanM2010Design, synthesis, and evaluation of dibenzo[c,h][1,6]naphthyridines as topoisomerase I inhibitors and potential anticancer agents. J. Med. Chem., 5324December 2010), 871687260022-2623'},{id:"B73",body:'KlamtAMennucciBTomasiJBaroneVCurutchetCOrozcoMLuqueF. J2009On the performance of continuum solvation methods. A comment on ‘universal approaches to solvation modeling’Acc. Chem. Res., 424April 2009), 4894920001-4842'},{id:"B74",body:'KmunicekJLuengoSGagoFOrtízA. RWadeR. CDamborskýJ2001Comparative binding energy analysis of the substrate specificity of haloalkane dehalogenase from Xanthobacter autotrophicus GJ10.Biochem., 4030July 2001), 890589170006-2960'},{id:"B75",body:'KmunicekJHyncováKJedlickaTNagataYNegriAGagoFWadeR. CDamborskýJ2005Quantitative analysis of substrate specificity of haloalcane dehalogenase Lin B from Sphingomonas paucimobilis UT26. Biochem., 4410March 2005), 339034010006-2960'},{id:"B76",body:'KollmanP. AMassovaIReyesCKuhnBHuoS2000Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models.Acc. Chem. Res., 3312December 2000), 8898970001-4842'},{id:"B77",body:'KuntzI. D1992Structure based strategies for drug design and discovery. Science, 2578August 1992), 107810820036-8075'},{id:"B78",body:'KuntzI. DMengE. CShoichetB. K1994Structure based molecular design. Acc. Chem. Res., 275May 1994), 1171230001-4842'},{id:"B79",body:'LiZLazaridisT2007Water at biomolecular binding interfacesPhys. Chem. Chem. Phys., 95February 2007), 5735811463-9076'},{id:"B80",body:'LinFWangR2010Systematic derivation of AMBER force field parameters applicable to zinc-containing systemsJ. Chem. Theory Comput., 66June 2010), 185218701549-9626'},{id:"B81",body:'LuchkoTGusarovSRoeD. RSimmerlingCCaseD. ATuszynskiJKovalenkoA2010Three-diemnsional molecular theory of solvation coupled with molecular dynamics in Amber. J. Chem. Theory Comput., 63March 2010), 6076241549-9626'},{id:"B82",body:'LumettaG. JRapkoB. MGarzaP. AHayB. P2002Deliberate design of ligand architecture yields dramatic enhancement of metal ion affinity.J. Am. Chem. Soc., 12420May 2002), 564456450002-7863'},{id:"B83",body:'MaJ. CDoughertyD. A1997The cation-π interaction. Chem. Rev., 975August 1997), 130313240009-2665'},{id:"B84",body:'ManceraR. L2007Molecular modeling of hydration in drug design.Curr. Opin. Drug. Discov. Dev., 103May 2007), 2752801367-6733'},{id:"B85",body:'MarcoENegriALuqueF. JGagoF2005Role of staking interactions in the binding sequence preferences of DNA bis-intercalators: insight from thermodynamic integration free energy simulations. Nuc. Ac. Res., 3319November 2005), 621462240305-1048'},{id:"B86",body:'MarcusYHefterG2006Ion pairing. Chem. Rev., 10611November 2006), 458546210009-2665'},{id:"B87",body:'MengE. CShoichetB. KKuntzI. D1992Automated docking with grid-based energy evaluationJ. Comput. Chem., 134May 1992), 5055240109-6987X'},{id:"B88",body:'MeyarE. ACastellanoR. KDiederichF2003Interactions with aromatic rings in chemical and biological recognition. Angew. Chem. Int. Ed., 4211March 2003), 121012501433-7851'},{id:"B89",body:'MirandaCEscartíFLamarqueLYuntaM. J. RNavarroPGarcía-espanaEJimenoM. L2004New 1H-pyrazole-containing polyamine receptor sable to complex L-glutamate in wáter at physiological pH values. J. Am. Chem. Soc., 1263January 2004), 8238330002-7863'},{id:"B90",body:'Miranda, C., Escartí, F., Lamarque, L., García-España, E., Navarro, P., Latorre, L., lloret, F., Jimenez, H.R. & Yunta, M.J.R. (2005). CuII and ZnII coordination chemistry of pyrazole-containing poliamine receptors- Influence of the hydrocarbon side chain length on the metal coordination. Eur. J. Inorg. Chem., Vol. 2005, No. 1, (January 2005), pp. 189-208. ISSN: 1434-1948'},{id:"B91",body:'MiriRJavidniaKHemmateenejadBAzarpiraAAmirghofranZ2004Synthesis, cytotoxicity, QSAR, and intercalation study of new diindenopyridine derivatives. Bioorg. Med. Chem., 1210May 2004), 252925360968-0896'},{id:"B92",body:'MishraP2010Biocoordination and computational modeling of streptomycin with Co(II), Ni(II), In(II) and inorganic Sn(II). Int. J. Pharm. Sci., 22June 2010), 87970097-6044X'},{id:"B93",body:'MobleyD. LBaylyC. ICooperM. DShirts & Dill, K.A. (2009Small molecule hydration free energies in explicit solvent: an extensive test of fixed-cahrge atomistic simulations. J. Chem. Theory Comput., 52February 2009), 3503581549-9626'},{id:"B94",body:'MoonJ. BHoweW. J1991Computer design of bioactive molecules: a method for receptor-based de novo ligands design. Proteins, 114December 1991), 3143280887-3585'},{id:"B95",body:'NichollsAWlodekSGrantJ. A2009The SAMP1 solvation challenge: Further lessons regarding the pitfalls of parameterization. J. Phys. Chem. B, 11314April 2009), 452145321089-5647'},{id:"B96",body:'OhK. SLeeC. WChoiH. SLeeS. JKimK. S2000Origin of the high affinity and selectivity of novel receptors for NH4+ over K+: Charged hydrogen bonds vs cation-π interaction.Org. Lett., 217August 2000), 267926811523-7052'},{id:"B97",body:'OnsagerL1936Electric moments of molecules in liquids, J. Am. Chem. Soc., 588August 1936), 148614930002-7863'},{id:"B98",body:'OrozcoMLuqueF. J2000Theoretical methods for the description of the solvent effect in biomolecular systemsChem. Rev., 10011November 2000), 418742260009-2665'},{id:"B99",body:'PalmerD. SFrolovA. IRatkovaE. LFedorovM. V2011Toward a universal model to calculate the solvation thermodynamics of druglaike molecules: The importance of new experimental databases. Mol. Pharm., 84August 2011), 142314290002-6895X'},{id:"B100",body:'ParkJ. YKimB. CParkS. M2007Molecular recognition of protonated polyamines at calix[4]crown-5 self-assembled monolayer modified electrodes by impedance measurements.Anal. Chem., 795March 2007), 189018960003-2700'},{id:"B101",body:'PastorinGDa Ros, T., Bolcato, C., Montopoli, C., Moro, S., Cacciari, B., Baraldi, P.G., varani, K., Borea, P.A. & Spalluto, G. (2006Synthesis and biological studies of a new series of 5-heteroarylcarbamoylaminopirazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidines as human A3 adenosine receptor antagonists. Influence of the heteroaryl substituent on binding affinity and molecular modeling investigations. J. Med. Chem., 495March 2006), 172017290022-2623'},{id:"B102",body:'PerezCPastorMOrtizA. RGagoF1998Comparative binding energy analysis of HIV-1 protease inhibitors: incorporation of solvent effects and validation as a powerful tool in receptor-based drug design.J. Med. Chem., 416March 1998), 8368520022-2623'},{id:"B103",body:'PetersM. BYangYWangBFüsti-molnárLWeaverM. NMerzK. MJr. (2010Structural survey of zinc-containing proteins and development of the zinc AMBER forcefield (ZAFF). J. Chem.Theory Comput. 69September 2010), 293529471549-9626'},{id:"B104",body:'PlewczynskiDLazniewskiMAugustyniacRGinalskiK2011Can we trust docking results? Evaluation of seven commonly used programs on PDB bind database. J. Comput. Chem., 324March 2011), 7427550109-6987X'},{id:"B105",body:'ReddyM. RErionM. DAgaewalA2000Use of free energy calculations in drug design, In: Reviews in computational chemistry 2. K.B. Lipkowitz & D.B. Boyd (Eds.), 217304978-0-47118-810-0'},{id:"B106",body:'ReddyM. RErionM. D2005Computer aided drug design strategies used in the discovery of fructose 1,6-biphosphate inhibitors. Curr. Pharm. Des., 113February 2005), 2832941381-6128'},{id:"B107",body:'ReddyA. SSastryG. MSastryG. N2007Cation-aromatic database.Proteins674March 2007), 41580887-3585'},{id:"B108",body:'ReddyM. RErionM. D2007Relative binding affinities of fructose-1,6-bisphosphatase inhibitors calculated using a quantum mechanics-based free energy perturbation method. J. Am. Chem. Soc., 12930August 2007), 929692970002-7863'},{id:"B109",body:'ReichertD. ENorrbyP-OWelchM. J2001Molecular modeling of bifunctional chelate peptide conjugates. 1. Copper and indium parameters for the Amber force field.Inorg. Chem., 4020September 2001), 522352300020-1669'},{id:"B110",body:'ReviriegoFNavarroPGarcía-espanaEAlbeldaM. TFriasJ. CDomenechAYuntaM. J. RCostaROrtíE2008Diazatetraester 1H-pyrazole crowns as fluorescent chemosensors for AMPH, METH, MDMA(Ecstasy) and dopamine. Org. Lett., 1022November 2008), 509951021523-7060'},{id:"B111",body:'ReynoldsC. AWadeR. CGoodfordP. J1989Identifying targets for bioreductive agents: using GRID to predict selective binding regions of proteins.J. Mol. Graph., 72June 1989), 1031080263-7855'},{id:"B112",body:'RiahiSEynollahiSGanjaliM. RNorouziP2010Computational modeling of interaction between Camphothecin and DNA base pairs. Int. J. Electrochem. Sci., 58August 2010), 115111631452-3981'},{id:"B113",body:'Rodríguez-ciriaM2000Síntesis De 1-aminoy14diamino derivados de benzo[g]ftalazina, evaluación de sus propiedades complejantes frente a cationes metálicos y catecolaminas involucrados en mecanismos de neurotrnasmisión. Ph.D. Thesis, Universidad Complutense, Madrid'},{id:"B114",body:'Rodríguez-ciriaMSanzA. MGómez-contrerasFNavarroPPardoMYuntaM. J. RCastineirasACanoM. C2002Benzo[g]phthalazine ligands as tyrosinase mimetics: the influence of the polyaminic side-chains size and nature on the complexation of Cu(II). Proceedings of 8th International symposium on the chemistry and pharmacology of pyridazines, Ferrara (Italy), October 2002'},{id:"B115",body:'Rodríguez-ciriaMSanzA. MYuntaM. J. RGómez-contrerasFNavarroPFernándezIPardoMCanoM2003Synthesis and cytostatic activity of N,N-bis-{3-[N-(4-chlorobenzo[g]-phthalazin-1-yl]aminopropil}-N-methylamine: a new potential DNA bisintercalator. Bioorg. Med. Chem., 1110May 2003), 214321480968-0896\n\t\t\t'},{id:"B116",body:'RoumenLPeetersJ. WEmmenJ. M. ABengelsI. P. ECustersE. M. GDe GooyerMPlateRPieterseKHilbersP. A. JSmitsJ. F. MVekemansJ. A. JLeysenDOttenheijmH. C. JJanssenH. MHermansJ. J. R2010Synthesis, biological evaluation, and molecular modeling of 1-benzyl-1H-imidazoles as selective inhibitors of aldosterone synthase (CYP11B2J. Med. Chem., 534February 2010), 171217250022-2623'},{id:"B117",body:'SakakuraKOkabeAOkuKSakuraiM2011Experimental and theoretical study on the intermolecular complex formation between trehalose and benzene compounds in aqueous solutionJ. Phys. Chem. B, 11532August 2011), 982398301089-5647'},{id:"B118",body:'Sanchez-morenoMSanzA. MGómez-contrerasFNavarroPMarínCRamírez-macíasIRosalesM. JOlmoFGarcía-arandaICampayoLCanoCArrebolaFYuntaM. J. R2011In vivo Trypanosomicidal activity of imidazole-or pyrazole-based venzo[g]phthalazine derivatives against acute and chronic phases of chagas disease. J. Med. Chem., 544February 2011), 9709790223-5234'},{id:"B119",body:'SandsZ. ALaughtonC. A2004Molecular dynamics simulations of DNA using the generalized Born solvation model: quantitative comparisons with explicit solvation resultsJ. Phys. Chem. B, 10828July 2004), 10113101191089-5647'},{id:"B120",body:'ShaikhS. AAhmedS. RJayaramB2004A molecular thermodynamic view of DNA-drug interactions: A case study of 25 minor-groove binders.Arch. Biochem. Biophys., 4291September 2004), 81990003-9861'},{id:"B121",body:'ShivakumarDWilliamsJWuYDammWShelleyJShermanW2010Prediction of absolute solvation free energies using molecular dynamics free energy perturbation and the OPLS force fieldJ. Chem. Theory Comput., 65May 2010), 150915191549-9626'},{id:"B122",body:'ShoichetB. KKuntzI. D1996Predicting the structure of protein complexes: a step in the right direction.Chem. and Biol., 33March 1996), 1511561074-5521'},{id:"B123",body:'SilvaS. JJayasunderaK2002Quantitative structure activity relationships for guanidiniothiazole carboxamides using theoretically calculated molecular descriptors. J. Natn. Sci. Found. Sri Lanka, 303-4December 2002), 1711841391-4588'},{id:"B124",body:'SimonsonT2001Macromolecular electrostatics: continuum models and their growing painsCurr. Opin. Struct. Biol., 112April 2001), 2432520095-9440X'},{id:"B125",body:'SlickersPHillebrandMKittlerLLöberGSühnelJ1998Molecular modeling and footprinting studies of DNA minor groove binders: bisquaternary ammonium heterocyclic compounds.Anti-Cancer Drug Des., 135September 1998), 4634880266-9536'},{id:"B126",body:'SoterasIMorrealeALópezJ. MOrozcoMLuqueF. J2004Group contributions to the solvation free energy from MST continuum calculationsBraz. J. Phys., 341March 2004), 48571678-4448'},{id:"B127",body:'SpäthAKönigB2010Molecular recognition of organic ammonium ions in solution using synthetic receptors.Beilstein J. Org. Chem., 632April 2010), 11111860-5397'},{id:"B128",body:'SrinivasEMurthyJ. NRaoA. R. RSastryG. N2006Recent advances in molecular modeling and medicinal chemistry aspects of phosphor-glycoprotein. Curr. Drug Metabol., 72February 2006), 2052171389-2002'},{id:"B129",body:'StoikaISadiqS. KCoveneyP. V2008Rapid and accurate prediction of binding free energies for saquinavir-bound HIV-1 proteases. J. Am. Chem. Soc., 1308February 2008), 263926480002-7863'},{id:"B130",body:'SubramanianGPaterliniM. GPortogheseP. SFergusonD. M2000Molecular docking reveals a novel binding site model for fentanyl at the µ-opioid receptor. J. Med. Chem., 433February 2000), 3813910022-2623'},{id:"B131",body:'TaylorR. DJewsburyP. JEssexJ. W2002A review of protein-small molecule docking methods.. J. Comput. Aid. Mol. Des., 163March 2002), 1511661573-4951'},{id:"B132",body:'TóthJRemkoMNagyM2005The ability of molecular modeling methods to reproduce the structure of flavonoids. Acta Facul. Pharm. Univ. Comenianae, Vol. LII, (2005), 2182250301-2298'},{id:"B133",body:'TschammerNElsnerJGoetzAEhrlichKSchusterSRubergMKühhornJThompsonDWhistlerJHübnerHGmeinerP2011Highly potent 5-aminotetrahydropyrazolopyridines: enantioselective dopamine D3 receptor binding, functional selectivity, and analysis of receptor-ligand interactions. J. Med. Chem., 547April 2011), 247724910022-2623'},{id:"B134",body:'Van GunsterenW. FBerendsenH. J. C1977Algorithms for macromolecular dynamics and constraint dynamicsMol. Phys., 345August 2006), 131113271362-3028'},{id:"B135",body:'VarnekAWipffGBilykAHarrowfieldJ. M1999Molecular dynamics and free energy perturbation studies of Ca2+/Sr2+ complexation selectivities of the macrocyclic ionophores DOTA and TETA in waterJ. Chem. Soc. Dalton Trans., 199923December 1999), 415541641472-7773'},{id:"B136",body:'VealJ. MLiXZimmermanS. CLambenmonC. RCoryMZonGWilsonW. D1990Interaction of a macrocyclic bisacridine with DNA.Biochem., 2949December 1990), 10918109270006-2960'},{id:"B137",body:'VenskutonyteRButiniSCocconeS. SGemmaSBrindisiMKumorVGuarinoEMaramaiSAmirAValadesE. AFrydenvangKKastrupJ. SNovellinoECampianiGPickeringD. S2011Selective kainite receptor (Gluk1) ligands structurally based upon 1H-cyclopentapyrimidin-2,4(1H,3H)-dione: Synthesis, molecular modeling, and pharmacological and biostructural characterization. J. Med. Chem., 5413July 2011), 479348050022-2623'},{id:"B138",body:'ViswanadhanV. NGhoseA. KSingU. CWendoloskiJ. J1999Prediction of solvation free energies of small organic molecules:additive-constitutive models based on molecular fingerprints and atomic constants.J. Chem. Inf. Comput. Sci., 392March 1999), 4054120095-2338'},{id:"B139",body:'WangJKangXKuntzI. DKollmanP. A2005Hierarchical database screenings for HIV-1 reverse transcriptase using a pharmacophore model, rigid docking and MM-PB/SA. J. Med. Chem.,488April 2005), 243224440022-2623'},{id:"B140",body:'WangHLaughtonC. A2009Evaluation of molecular modeling methods to predict the secuence-selectivity of DNA minor groove binding ligands. Phys. Chem. Chem. Phys.. 1145December 2009), 10722107281463-9076'},{id:"B141",body:'WangHLaughtonC. A2010Molecular modeling mrthods to quantitative drud-DNA interactions, In: Drug-DNA interaction protocols, Methods in molecular biology, 6131931Humana Press, Germany. 978-1-60327-417-3'},{id:"B142",body:'WeinerS. JKollmanP. ACaseD. ASinghV. CGhioCAlagonaGProfetaSJr. & Weiner, P. (1984A new force field for molecular mechanical simulation of nucleic acids and proteinsJ. Am. Chem. Soc., 1063February 1984), 7657840002-7863'},{id:"B143",body:'WeinerS. JKollmanP. ANguyenD. TCaseD. A1986An all atom force field for simulations of proteins and nucleic acidsJ. Comput. Chem., 72April 1986), 2302520109-6987X'},{id:"B144",body:'WilsonCMaceJ. EAgardD. A1991A computational method for designing enzymes with altered substrate specifity. J. Mol. Biol., 2202July 1991), 4955060022-2836'},{id:"B145",body:'WoodsR. JDwekR. AEdgeC. JFraser-reidB1995Molecular mechanical and molecular dynamical simulations of glycoproteins and oligosaccharides. 1. GLYCAM_93 parameter developmentJ. Phys. Chem., 9911March 1995), 383238460022-3654'},{id:"B146",body:'YangLTanCHsiehM-JWangJDuanYCieplakPCaldwellJKollmanP. ALuoR2006New generation Amber united-atom force field. J. Phys. Chem. B, 11026July 2006), 13166131761089-5647'},{id:"B147",body:'ZachariasNDoughertyD. A2002Cation-π interactions in ligand recognition and catalysis. Trends Pharm. Sci., 236June 2002), 2812870165-6147'},{id:"B148",body:'ZgarbováMOtyepkaMSponerJMládekABanésPCheathamT. EIII & Jurecka, P. (2011Refinement of the Cornell et al. nucleic acids force field based on reference quantum chemical calculations of glycosidic torsion profilesJ. Chem. Theory Comp., 79September 2011), 288629021549-9626'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"María J. R. Yunta",address:null,affiliation:'
Sport for Development and Peace (SDP) is an international movement that began in the 2000s to meet the Millennium Development Goals (2000–2015). Several local, regional, national and international organizations are currently continuing to implement sports projects in an international development context to reach the United Nations’ sustainable development goals (2015–2030).
\n
This chapter aims to present the various origins and objectives that are being used around the SDP. It then focuses on current research on SDP, providing illustrations of research projects conducted in the field. Finally, this chapter offers perspectives for future research in this domain.
\n
\n
1.1 Origins and history of the SDP movement
\n
Sport for Development and Peace (SDP) is not a new phenomenon contrary to what one might think. In 1894, Pierre de Coubertin had already considered the reconstruction of the modern Olympic Games to bring nations closer together around sports disciplines. He said “I remained convinced that sport is one of the most forceful elements of peace and I am confident in its future action” [1]. But the use of sport to serve development, peace, or diplomatic interests in the contemporary world is more due to the work of Mandela, who said “Sport has the power to change the world. It has the power to inspire, it has the power to unite people in a way that little else does” [2]. Indeed, the South African leader decided to use the power of sport during the 1995 Rugby World Cup to fight apartheid and unite the South African people. According to him, “Sport can create hope, where once there was only despair. It is more powerful than governments in breaking down racial barriers” [2].
\n
The United Nations (UN) took a step further toward the recognition of sport and its diplomatic, integrative, educational, or peace-building potential by signing a resolution in favor of the use of sport as a tool for development and peace-building among peoples, which was adopted by the UN General Assembly in 2003. This vote also led to the reaffirmation in 2015 of the 1978 UNESCO International Charter for Physical Education and Sport. The prevalence of SDP projects was so high that the UN has recognized its potential by setting up a specific instance between 2008 and 2017 (United Nations Office for Sport and Development and Peace; UNOSDP) through which it has initiated a large number of projects, particularly in Central America and West Africa [3]. This office had three main roles: to encourage dialogue, to establish SDP collaborations and partnerships, and to support international sports organizations, civil society, private sector, and media.
\n
\n
\n
1.2 Definition and objectives of the SDP
\n
SDP projects have been developing in recent years around the world. They have been defined as “the intentional use of sport, physical activity and play to achieve specific development objectives in low- and middle-income countries and disadvantaged communities in high-income areas” [4], which includes “all forms of physical activity that contribute to physical fitness, mental well-being and social interaction, such as play, recreation, organized or competitive sport, indigenous sports and games” [4, 5]. These definitions have since been widely used by many SDP actors and several researchers [5, 6, 7].
\n
In these initiatives, sport is presented as a lever for integration or social reintegration in developing countries or in conflict-affected areas [7, 8]. For example, soccer matches are used between two enemy sides to help rebuild relationships. In addition to its positive impact on health, sport is now recognized for having a number of other benefits such as the prevention of violence or doping, awareness of diseases such as HIV/AIDS, and also as a medium for instilling respect for opponents and rules, teamwork, sportsmanship, determination, and discipline, in youth [7, 8]. These fundamental principles could also be transferred to the social life of person according to some organizations that value them [9]. The UNOSDP [10] indicates other elements related to the use of sport as a lever for development and peace, among others:
Sport is a powerful tool with unique power to attract, mobilize, and inspire;
Sport embodies issues of participation, inclusion, and citizenship by its very own nature;
It represents human values such as respect for the opponent, acceptance of restrictive rules, teamwork, and equity;
Sport is used in a very wide range of situations to serve development and peace-building as an integrated instrument in short-term emergency humanitarian aid activities or in long-term development cooperation projects [11, 12].
\n\n
Finally, sport has benefits such as individual development, health promotion and disease prevention, gender equality, social integration, peace-building or conflict prevention/resolution and post-disaster/trauma assistance [13, 14]. UNESCO published a report in 2016 on the power of the values of sport that reinforces this vision, and then UNOSDP published a document that shows the articulation of using sport to support each of the new Sustainable Development Goals 2015–2030 [10]. From a development perspective, the focus is most of the time on mass sport and not elite sport [15, 16]. In a development context, sport generally includes a wide range of activities adapted to people of all ages and abilities, with an emphasis on the positive values of sport [10]. Sport is used to reach the most needy, including refugees; child soldiers; victims of conflict and natural disasters; poor people; people with disabilities; and victims of racism, stigma, and discrimination [14, 17, 18].
\n
\n
\n
\n
2. Current researches on SDP
\n
Beyond descriptions of SDP programs and contributions from international organizations, researchers examined the SDP field and analyze the benefits of these programs on individual development, health promotion and disease prevention, gender equality promotion, social integration, peace-building or conflict prevention and resolution, and assistance after a disaster or trauma, among others [13, 14]. At the moment, four main types of research that have been conducted around SDP can be identified: (1) macrosociological studies on the positive attributes of SDP; (2) exploratory field and case studies; (3) studies on the management and evaluation of SDP programs; and (4) literature reviews on SDP.
\n
\n
2.1 Macrosociological studies on the SDP
\n
First, researchers are conducting a large number of macrosociological studies to question the so-called positive attributes of sport by raising its potential abuses [11, 12, 19, 20, 21]. For example, Kidd [14, 22] conducted extensive literature reviews describing the landscape of the SDP movement. According to the author, SDP initiatives were motivated by athlete activism, the reaction to the fall of apartheid and made openings possible by the end of the Cold War, the neoliberal emphasis on entrepreneurship and mass mobilizations for “Make Poverty History,” as part of a major focus of UN political development and the SDP International Working Group [14, 22]. The current results of these global studies show that despite the potential benefits of sport, these positive social impacts do not automatically accumulate. Achieving positive impacts require professional and socially responsible interventions that are adapted to the social and cultural context, prioritize development objectives, and are carefully designed to be inclusive [10, 17, 23]. Nevertheless, some authors note the lack of scientific literature regarding the understanding of the specific mechanisms by which sport can foster development and peace among participants [9, 24, 25].
\n
\n
\n
2.2 Exploratory field and case studies on the SDP
\n
Second, some researchers have used several exploratory methodologies to conduct field case studies [26, 27, 28]. For example, Oxford [27] focused on the social inclusion of young Colombian women through football, a traditionally very male sport. The researcher conducted a 6-month ethnographic study in Colombian neighborhoods of the SDP organization to explore the social, cultural, and historical complexities surrounding the safe practice of girls’ sports. Whitley et al. [28] attempted to question key players in SDP about their experiences and expertise in the field. The study provided a better understanding of the limit, the lack of efficiency and equity in practices as well as a concrete impact that they felt was unclear. The study concludes with a list of recommendations to improve SDP field work, research partnerships, and evaluation collaborations in a more rigorous way. Finally, some authors such as Gadais et al. also aim to develop research methods adapted to the SDP field, which is often unstable, complex, or unsafe [26]. The authors intended to implement analyses and methods from a distance and on the field to better understand SDP organizations and their needs in order to better support them in their work.
\n
\n
\n
2.3 Management and evaluation of SDP programs
\n
Third, researchers are also interested in questions of program evaluation and management of SDP activities. On the one hand, SDP organizations are frequently approached by the funding agencies to conduct SDP program evaluation studies. This is a classic way of observing the impact of sport on social change [29, 30, 31]. The evaluation studies examined various aspects of the missions and paradigms of SDP projects [30, 32, 33]. A literature review conducted by Levermore [30] revealed three major limitations to SDP evaluation studies: (a) monitoring and evaluation are insufficient; (b) they are conducted with acclaimed programs; and (c) they tend to use a positivist logical framework (Levermore [30]). Levermore concluded his analysis by stressing the need for evaluations that can take into account the diversity of SDP projects, some of which have unclear objectives or missing justifications. Indeed, their objectives and strategies remain unclear and questionable in relation to fully implemented program evaluation protocols [30, 34]. Programs should be evaluated using solid methodological documentation on logical frameworks and critical participatory approaches to try to apply these approaches to specific case studies or to consider their use in the context of a particular sporting event [30]. On the other hand, some researchers aim to strengthen the managerial aspects of SDP projects to improve their functioning, management, or implementation mechanisms [34, 35, 36, 37]. Often, the overall idea is to build connections between the theory generated by macrosociological studies and field case studies. Sport management specialists have begun to critically review and evaluate SDP initiatives, and they are now more strategically planned and pedagogically solid than before. For example, Schulenkorf [37] reviewed the main achievements of sport management research and classifies current research under four headings: (a) SDP programming and design; (b) sustainable management and capacity-building; (c) creation and optimization of impacts and outcomes; and (d) conceptual/theoretical advances. Finally, he suggested that future research could focus on the managerial concepts of leadership, entrepreneurship, and design thinking to maximize the potential of sport (management) to contribute to desired, innovative, and sustainable outcomes for community development.
\n
\n
\n
2.4 Literature reviews on SDP
\n
Fourth, three literature reviews have been conducted on SDP. Until 2016, there was little research to synthesize research on SDP. There was no mapping to know what projects existed and to have an overview of the situation at the global level. In 2017, the review conducted by Svensson and Woods [38] addressed this gap by providing a systematic overview of SDP organizations. While the precise locations of action of SDP organizations remain largely unknown, this review has focused these efforts and on the physical and sporting activities used in the programs. It provided an opportunity to review the practice of SDPs in order to provide an overview of the current state of the field: 955 entities involved in SDP practices were identified based on a systematic review of 3138 organizational entries in the SDP databases. The majority of organizations operate programs in Africa, but many are present in Europe, North America, Asia, and Latin America, with more than 80% of them having their headquarters in the same region. Education, livelihoods, and health emerged as the most common themes, while disability and gender were less represented. A total of 32 types of sports have been identified, one-third is only based on football (soccer). In relation to positive youth development (PYD) through sport, Jones et al. [39] conducted an analysis of how sport is a mechanism for achieving various development objectives. The review shows that this link between sport and development is not inherent and depends not only on a variety of programs and activities but also on contextual factors. The positive potential of sport does not develop automatically; it requires a professional and socially responsible intervention, adapted to the social and cultural context [17, 23, 30]. Finally, Schulenkorf et al. [8] conducted an integrated analysis of the literature on sport for development to provide a comprehensive and holistic picture of the sector. Despite the significant increase in published research in the field of sport for development, there has been no attempt to rigorously review and synthesize scientific contributions in this field so far. The paper shows an upward trend in scientific publications since 2000, with an emphasis on social and educational outcomes related to youth sport, with football (soccer) being the most common activity. The vast majority of SDP research has been conducted at the community level, where qualitative approaches dominate (70% of conceptual and qualitative methods). The authors also noted an interesting paradox regarding the geographical contexts of the studies: a majority of the projects are carried out in Africa, Asia, and Latin America, but 74% of the study fields and 90% of the SDP authors are based in North America, Europe, and Australia.
\n
\n
\n
2.5 SDP research themes
\n
According to the Journal of Sport for Development, several research themes have been identified in relation to SDP (Table 1).
\n
\n
\n
\n\n
\n
Thematics
\n
Descriptions
\n
\n\n\n
\n
Sport and disability
\n
Sport and disability focuses on research related to sport as a vehicle for the development, access, inclusion, and human rights of people with disabilities. This section encourages critical thinking and diversity of perspectives, welcoming research at the intersection of theory and practice.
\n
\n
\n
Sport and education
\n
Sport and education presents research and case studies related to interventions that use sport to advance education, youth development, and life skills. Rather than focusing on sport education, this section discusses the role of sport in achieving the academic and social outcomes of youth.
\n
\n
\n
Sport and gender
\n
The theme on sport and gender presents research and case studies related to interventions using sport to promote gender equality, challenge gender norms, and empower girls and women in disadvantaged environments.
\n
\n
\n
Sport and health
\n
Sport and health presents a wide range of outcomes associated with physical, mental, and social well-being. This is the effect of SDP programs on the risk factors for communicable and non-communicable diseases, including the direct effect of sports programs on physical activity. It also examines the role that sport can play in preventive education and health promotion interventions.
\n
\n
\n
Sport and livelihoods
\n
The theme on sport and livelihoods presents research and case studies on interventions using sport to improve the livelihoods of disadvantaged people, from programs focusing on vocational skills training to rehabilitation and social enterprise.
\n
\n
\n
Sport and peace
\n
Sport and peace focuses on projects that use sport as a vehicle for reconciliation and peace-building. The concept of peace is broadly defined to include connotations of personal, community, and social well-being, as well as the absence of conflict and tension between groups. In particular, this section examines the possibilities of creating peace between individuals and groups in socially, culturally, or ethnically divided societies.
\n
\n
\n
Sport and social cohesion
\n
The sport and social cohesion theme includes projects in the areas of community empowerment, social inclusion/integration, and diversity management. It focuses on social impact assessments and capacity-building initiatives that can lead to social cohesion, skills enhancement, and overall community development.
\n
\n\n
Table 1.
Research themes related to the SDP field.
\n
\n
\n
\n
3. Illustrations of SDP research projects
\n
\n
3.1 Education, social inclusion, and environment: Bel Avenir (Madagascar)
\n
Bel Avenir (BA) is a Malagasy NGO working in the southern region of Madagascar, through social projects, focusing on “education as a vehicle of development.” BA carries out activities in various fields of education for young disadvantaged populations in Madagascar, particularly in Toliara and Fianarantsoa. The field of education includes: (a) formal education in two schools, (b) non-formal education including a school of sports and a music and arts center, among others, (c) awareness-raising projects, such as international inter-school exchanges, or publications of Malagasy stories. Thus, the organization offers a holistic approach to education for development and the SDP proposed by its school of sports, which is only one of its various services. The country is severely affected by extreme poverty, malnutrition, severe hygiene and health problems, child labor problems (mining or prostitution), corruption in society, and frequent political crises. In this sense, BA works in a complex context, most often difficult, unstable, and sometimes insecure, where reality could be ephemeral. BA is finally a member of the international network Agua de Coco, based in eight countries, and mobilized around children’s rights.
\n
Two research projects are currently running to support and strengthen BA’s projects. The first study attempts to develop a methodology that uses the Actantial Model [40] and the Snakes and Ladders [7] to analyze and understand the NGO’s situation from a distance [41]. By using the NGO’s annual reports and comparing them to reality, the researchers are developing a methodology to verify whether a research can be successfully conducted in collaboration with the local organization. A second study, focusing on the needs of the NGO, aims to measure the effects of sports (school of sports) and artistic activities (arts and music center) [42] in order to understand their consequences on the psychological and social well-being of disadvantaged youth. This research also aims to strengthen monitoring and evaluation tools for young people and to set up a psychological unit to monitor young people in their development.
\n
\n
\n
3.2 Training of life and sports coaches—Pour 3 points (Canada)
\n
The non-profit organization Pour 3 points (P3P), established in Montreal, Canada, since 2013, uses sport as a tool to promote the development of youth in socio-economically disadvantaged neighborhoods. More specifically, P3P offers a 2-year life coaching training program for young Canadians who are interested in coaching and are willing to make a long-term commitment to the program and to disadvantaged communities. Their role is to learn how to support young people in their lives and to help them to avoid dropping out of primary or secondary school, and to support those who experience learning problems or have serious behavioral problems. By being well trained, coaches can help young people develop the skills they need to succeed in school and in their life. After parents, coaches are the most influential adults in the lives of young athletes according to P3P. This influence is felt not only in the teaching of the game but also in the teaching of life.
\n
Coaches are recruited at the time of enrolment in the training program, based on the skills required to become life coaches while becoming sport coach in one of the organization’s partner schools. Each year, the program recruits approximately 15 coaches who participate in a 4-day training retreat, five peer discussion circles, five formal training sessions, and three personal evaluations each year, all under the supervision of a development consultant.
\n
Several research projects have been conducted with P3P. A first study conducted on the P3P training program [43], examined coaches’ perceptions based on a humanist coaching workshop they received in their training. The results revealed that coaches perceive positive results in autonomy, communication, skills, motivation, and willingness to help their athletes’ teammates. A second study was conducted to strengthen the organization’s logic model to identify indicators for subsequent program evaluation. The results showed differences in the understanding of the program between key stakeholders. Recommendations from research allowed P3P administrators to reframe their theory of change [44]. This study was designed in collaboration with P3P administrators to help them improve their logic model and prepare their program evaluation. The idea for this research came directly from the P3P administrators and the researchers acted as facilitators.
\n
\n
\n
\n
4. Axis of tensions between practice and theory of SDP
\n
Several tensions can be noted between the needs of practitioners and their realities on the field with the possibilities of SDP research. The aim is to identify them and then propose a plan for action and research (Table 2).
\n
\n
\n
\n
\n\n
\n
SDP practice
\n
Axis of tensions
\n
SDP theory or research
\n
\n
\n
Practical needs of SDP
\n
Needs for research
\n
\n\n\n
\n
Evaluate effects or impacts of the SDP projects
\n
\nProgram evaluation\n
\n
Need for indicators/criteria to conduct evaluation
\n
\n
\n
Projects are imperfect and need be improve
\n
\nCritic/support\n
\n
Need to critic projects but also support actors and organizations
\n
\n
\n
Reinforce administration team and management work
\n
\nManagement\n
\n
Need to reinforce management elements of projects
\n
\n
\n
What is the finality/use/form of SDP?
\n
\nFinality/use\n
\n
Need to identify the types of SDP and needs about thematics
\n
\n
\n
What is the qualification/training of SDP personal/staff
\n
\nTraining/workshop\n
\n
Need for research on training
\n
\n
\n
Reality field could be unsecure, unstable, complex, dangerous
\n
\nMethod/tools\n
\n
Need to improve quality of research and have adapted tools for investigation
\n
\n\n
Table 2.
Tensions between practice and theory on SDP.
\n
First, we can observe a first axis of tension around program evaluation. On the one hand, SDP organizations are often asked by their donors to conduct program evaluations. This allows them to justify the rationale for their projects and to demonstrate the effectiveness of their actions. However, if these evaluations are not well planned, negative results can be found that compromise projects. SDP organizations often call on researchers to help them conduct their program evaluation because it is a time-consuming process. On the other hand, researchers need precise and specific criteria to conduct a relevant program evaluation. Unfortunately, few projects are able to provide evaluators with these very important indicators to conduct a fair and meaningful evaluation.
\n
Second, SDP projects are rarely perfect in their planning and implementation because they face limited resources and highly changing contexts. As well, it is necessary for administrators to make constant adjustments to improve the implementation and realization of their projects. While SDP projects are criticized by researchers in demonstrating several nonsense between the aims and actions of the project, it remains true that researchers would also benefit from offering a support and collaboration service to try to solve the field difficulties encountered by the actors.
\n
Thirdly, another axis of tension can be detected on the managerial aspects of SDP projects. On the one hand, the administrations of organizations are increasingly developing with their projects. As they do so, they must strengthen their structure and organization, which is often dependent on the financial and human resources at their disposal. On the other hand, researchers have started to conduct several studies to better understand the managerial aspects of SDP organizations, and it would be relevant if these studies could strengthen the organizational aspects of SDP projects which often do not have much support.
\n
Fourthly and for the time being, few differences have been made in SDP projects between those aimed at elite sport, competition, physical education, physical activity for leisure, or another theme such as health education through SDP. In our opinion, there is a very important tension about the purpose, use, and form that the SDP can represent and be truly in field projects. While several texts have been written to attempt to highlight these elements, few studies have attempted to go further in understanding what the SDP really is. This research seems essential to us to make the difference between the various forms of SDP and their multiple uses. This will eventually make it possible to identify new themes to investigate around the SDP.
\n
Fifth, there are currently many questions around who are the people who work with the populations in SDP, what are their training or qualifications? While the research strongly recommends the use of sport supervised by qualified and trained personnel, few studies have focused on the profiles and the training of those people who work in the field every day. On this axis of tension, research must propose areas of response to strengthen field actions. And on this point, it is therefore necessary for researchers to go down to the field to see and understand the reality of the projects.
\n
Finally, SDP fields are often dangerous and unsafe as they are located in humanitarian crisis or international development situations. These situations can change in a few minutes and working in this environment is therefore extremely unstable. They also face very complex realities in which it is necessary to take into account as many elements as possible in order to operate. Faced with the reality of this type of terrain, researchers must adapt their work. In particular, research methods and tools must evolve to adapt to a changing reality and to conditions that are sometimes very inappropriate for conducting a traditional research project. These adaptations are necessary to improve the quality of research in SDP’s fields.
\n
\n
\n
5. Future research perspectives on the SDP
\n
SDP research now offers a better understanding of the movement and allows practitioners to better orient themselves in their use of sport for development. However, the research also raised a set of concrete issues for field projects and some questions remain unanswered at this time. Following the results of the latest studies, six main areas of work should be considered to guide further research on SDP.
Provide a space for reflection (criticize vs. support): current research is often critical of SDP projects and too rarely supports or improves the action of actors in the field. However, it seems important to strengthen the work of the actors while continuing to question their actions and achievements. In this sense, the researcher must offer a space for joint reflection with the actors in the field;
Use a collaborative or partnership approach to conduct research (be a facilitator): one of the roles of research is to help solve practitioners’ problems. Specifically in the domain of SDP, field actors express difficulties and needs that must be listened in order to co-construct research projects. In this sense, the researcher should act as a facilitator to support the projects and the work of the actors while continuing to criticize them in his/her support;
Starting from the concrete angle of the field: to be able to fully understand the nuances of the context and/or the environment of the SDP actors, researchers are invited to be as close as possible to reality, and to step into the field as possible. This element is essential to build a relationship of trust with the actors to help them by understanding their background and endings as much as possible;
Seek interdisciplinary research: SDP themes are complex and often overlap with scientific knowledge from several research fields (e.g., sociology, psychology, and education). Researchers from several scientific disciplines must be open and work together as much as possible, in order to have the most precise and complex understanding of the phenomena that are difficult to capture from a single angle. Research must provide a better understanding of the multiple issues and the complexity of the issues, problems, and realities;
Propose better quality of research: it also seems relevant to us to question how to carry out better quality research on ephemeral or unstable fields, when access is considered complex and dangerous. This requires, among other things, the development of methods able to adapt and respond to the requirements of the domain as well as to the various fields of investigation;
Clarify the uses of SDP: finally, it seems essential to us to question the type of sport for development and peace that is used in the various contexts of SDP. More specifically, is it competitive sport, physical education, physical activity, health education, or any other form? On this subject, Hills et al. [45] had opened up interesting avenues for reflection by mentioning sport + and + sport [46], sport for social inclusion [24], sport as a universal language [1, 24], sport as a diversion [47], as a replacement or alternative [48], as a hook [49, 50] or for life skills [51, 52], among others.
\n\n
\n
\n
6. Conclusion
\n
This chapter aimed to present the field of SDP, its origins, its evolution, the research that has been carried out so far, as well as illustrations to give the reader a better idea of what “Sport for Development and Peace” is. However, answering the question “what is the SDP?” is not easy given that this field is vast, complex, and constantly changing in practice.
\n
In conclusion, three main elements can be remembered: (1) a large number of projects and programs have been developed since the 2000s, mainly in Africa, Latin America, and Asia, with football being the main sport [8, 38]. Other various forms of physical activity and sports (e.g., physical education, competitive sport, and leisure activities) have also been used in order to achieve development or peace and related topics; (2) research on SDP has intensified since 2010 [8]; and it can be grouped into four main categories of studies: macrosociological, exploratory field studies, managerial and program evaluation, and literature reviews; (3) several challenges and tensions remain to be resolved in order to accomplish quality research that will truly help and support actors from the field who use SDP.
\n
We can finally return to the proposals of Baron de Coubertin and Mandela, who were very visionary in using sport as a vehicle for development and as a means of establishing peace. Because today, many organizations such as the United Nations prefers to rely on the universal potential of sport or other non-formal recreation to resolve conflicts and educate future generations, rather than traditional institutions such as schools or governments.
\n
\n
Acknowledgments
\n
The author would like to acknowledge all research collaborators (Arvisais, O., Ayoub, M-B., Bardocz-Bencsik M., Belanger, C., Charland, P., Caicedo, J-C., Dalcourt-Malenfant, S., Decarpentrie, L., Falcão W. Parlavecchio, L., Rouzaut, M., Varela, N., and Webb, A.) and also send a special thanks to all field partners of SDP researches (Bel Avenir, Escuela de communidad—Cuidad Bolivar, P3P, Conseil de Bande des Premieres Nations d’Opitciwan).
\n
Conflict of interest
The author declares no conflict of interest.
\n',keywords:"sport for development, sport for peace, sport for education, sport for health, international",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/69149.pdf",chapterXML:"https://mts.intechopen.com/source/xml/69149.xml",downloadPdfUrl:"/chapter/pdf-download/69149",previewPdfUrl:"/chapter/pdf-preview/69149",totalDownloads:433,totalViews:0,totalCrossrefCites:0,dateSubmitted:"June 11th 2019",dateReviewed:"August 15th 2019",datePrePublished:"November 18th 2019",datePublished:"December 23rd 2020",dateFinished:"September 20th 2019",readingETA:"0",abstract:"Sport for Development and Peace (SDP) is an international movement that began in the 2000s with the Millennium Development Goals (2000–2015) and is currently continuing around the United Nations’ Sustainable Development Goals 2015–2030, driven by international organizations such as UNESCO. Often located in an international development context, organizations and associations use sport as a vehicle to reach several social and humanitarian missions (e.g., education, social cohesion, health, reintegration, diplomacy, and peace). This chapter presents the origins and objectives of the SDP, but it also looks at current research in the field. Since 2010, studies have significantly increased in the field around four main areas (macrosociological, field explorations, program management and evaluation, and literature reviews). This chapter also provides illustrations of SDP research projects, axis of tensions between practice and theory, and perspectives for future research in the field.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/69149",risUrl:"/chapter/ris/69149",signatures:"Tegwen Gadais",book:{id:"9158",title:"Sports Science and Human Health",subtitle:"Different Approaches",fullTitle:"Sports Science and Human Health - Different Approaches",slug:"sports-science-and-human-health-different-approaches",publishedDate:"December 23rd 2020",bookSignature:"Daniel Almeida Marinho, Henrique P. Neiva, Christopher P. Johnson and Nawaz Mohamudally",coverURL:"https://cdn.intechopen.com/books/images_new/9158.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"177359",title:"Dr.",name:"Daniel Almeida",middleName:"Almeida",surname:"Marinho",slug:"daniel-almeida-marinho",fullName:"Daniel Almeida Marinho"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"308043",title:"Prof.",name:"Tegwen",middleName:null,surname:"Gadais",fullName:"Tegwen Gadais",slug:"tegwen-gadais",email:"gadais.tegwen@uqam.ca",position:null,institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_1_2",title:"1.1 Origins and history of the SDP movement",level:"2"},{id:"sec_2_2",title:"1.2 Definition and objectives of the SDP",level:"2"},{id:"sec_4",title:"2. Current researches on SDP",level:"1"},{id:"sec_4_2",title:"2.1 Macrosociological studies on the SDP",level:"2"},{id:"sec_5_2",title:"2.2 Exploratory field and case studies on the SDP",level:"2"},{id:"sec_6_2",title:"2.3 Management and evaluation of SDP programs",level:"2"},{id:"sec_7_2",title:"2.4 Literature reviews on SDP",level:"2"},{id:"sec_8_2",title:"2.5 SDP research themes",level:"2"},{id:"sec_10",title:"3. Illustrations of SDP research projects",level:"1"},{id:"sec_10_2",title:"3.1 Education, social inclusion, and environment: Bel Avenir (Madagascar)",level:"2"},{id:"sec_11_2",title:"3.2 Training of life and sports coaches—Pour 3 points (Canada)",level:"2"},{id:"sec_13",title:"4. Axis of tensions between practice and theory of SDP",level:"1"},{id:"sec_14",title:"5. Future research perspectives on the SDP",level:"1"},{id:"sec_15",title:"6. Conclusion",level:"1"},{id:"sec_16",title:"Acknowledgments",level:"1"},{id:"sec_19",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'\nde Coubertin P. Le rétablissement des Jeux olympiques. Revue de Paris; 1894. p. 15\n'},{id:"B2",body:'\nMandela N. Speech by Nelson Mandela at the Inaugural Laureus Lifetime Achievement Award. Monaco, Monte Carlo: Inaugural Laureus Lifetime Achievement Award; 2000\n'},{id:"B3",body:'\nUNESCO. Sport for development and peace. 2016. Available from: http://www.unesco.org/new/en/social-and-human-sciences/themes/physical-education-and-sport/sport-forpeace-and-development/ [Accessed June 2019]\n'},{id:"B4",body:'\nUN Inter-Agency Task Force on Sport for Development and Peace. Sport as a Tool for Development and Peace - the United Nations; 2003\n'},{id:"B5",body:'\nRichards J, Kaufman Z, Schulenkorf N, Wolff E, Gannett K, Siefken K, et al. Advancing the evidence base of sport for development: A new open-access, peer-reviewed journal. Journal of Sport for Development. 2013;1(1):1-3\n'},{id:"B6",body:'\nSchulenkorf N, Adair D. Global Sport-for-Development : Critical Perspectives. New York: Palgrave Macmillan; 2014\n'},{id:"B7",body:'\nWebb AJ, Richelieu A. Sport for development and peace snakes and ladders. Qualitative Market Research. 2015;18(3):278-297\n'},{id:"B8",body:'\nSchulenkorf N, Sherry E, Rowe K. Sport for development: An integrated literature review. Journal of Sport Management. 2016;30(1):22-39\n'},{id:"B9",body:'\nLevermore R. Sport a new engine of development? Progress in Development Studies. 2008;8(2):183-190\n'},{id:"B10",body:'\nUnited Nations Office on Sport for Development and Peace. Sport and Sustainable Development Goals; 2017\n'},{id:"B11",body:'\nCoalter F. Sport-for-development: Going beyond the boundary? Sport in Society. 2010;13(9):1374-1391\n'},{id:"B12",body:'\nDarnell S. Power, politics and “sport for development and peace”: Investigating the utility of sport for international development. Sociology of Sport Journal. 2010;27(1):54-75\n'},{id:"B13",body:'\nChawansky M, Holmes M. Sport, social development and peace. Sport in Society. 2015;18(6):752-756\n'},{id:"B14",body:'\nKidd B. A new social movement: Sport for development and peace. Sport in Society. 2008;11(4):370-380\n'},{id:"B15",body:'\nBlack DR. The ambiguities of development: Implications for development through sport. Sport in Society. 2010;13(1):121-129\n'},{id:"B16",body:'\nKidd B. Literature Reviews on Sport for Development and Peace. Toronto: Commissioned by SFD IWG Secretariat; 2007\n'},{id:"B17",body:'\nHartmann D, Kwauk C. Sport and development: An overview, critique, and reconstruction. Journal of Sport and Social Issues. 2011;35(3):284-305\n'},{id:"B18",body:'\nInternational Working Group Sport for Development and Peace. Harnessing the Power of Sport for Development and Peace: Recommendations to Governments. Toronto: Sport for Development and Peace International Working Group; 2008\n'},{id:"B19",body:'\nBeutler I. Sport serving development and peace: Achieving the goals of the United Nations through sport. Sport in Society. 2008;11(4):359-369\n'},{id:"B20",body:'\nDarnell S. Sport for Development and Peace: A Critical Sociology. London: Bloomsbury Academic; 2013\n'},{id:"B21",body:'\nYoung K, Okada C. Introduction: Sport, social development and peace: Acknowledging potential, respecting balance. In: Research in the Sociology of Sport. Emerald Group Publishing Ltd.; 2014. pp. ix-xxix\n'},{id:"B22",body:'\nKidd B. A new social movement: Sport for development and peace. In: Jackson SJ, Haigh S, editors. Sport and Foreign Policy in a Globalizing World. London: Taylor and Francis; 2013. pp. 22-32\n'},{id:"B23",body:'\nGardam K, Giles AR, Hayhurst LMC. Understanding the privatisation of funding for sport for development in the Northwest Territories: A Foucauldian analysis. International Journal of Sport Policy. 2017;9(3):541-555\n'},{id:"B24",body:'\nGreen BC. Sport as an agent for social and personal change. In: Girginov V, editor. Management of Sports Development. Oxford: Butterworth-Heinemann; 2008. pp. 129-147\n'},{id:"B25",body:'\nHartmann D. Theorizing sport as social intervention: A view from the grassroots. Quest. 2003;55:118-140\n'},{id:"B26",body:'\nGadais T, Webb A, Garcia A. Using report analysis as a sport for development and peace research tool: The case of El Salvador Olimpica Municipal’s programme. Journal of Sport for Development. 2017;6(10):12-24\n'},{id:"B27",body:'\nOxford S. The social, cultural, and historical complexities that shape and constrain (gendered) space in an SDP organisation in Colombia. Journal of Sport for Development. 2017;6(10):1-11\n'},{id:"B28",body:'\nWhitley MA, Farrell K, Wolff EA, Hillyer SJ. Sport for development and peace: Surveying actors in the field. Journal of Sport for Development. 2019;7(11):1-15\n'},{id:"B29",body:'\nKaufman Z, Rosenbauer BP, Moore G. Lessons learned from monitoring and evaluating sport-for-development programmes in the Caribbean. In: Global Sport-for-Development. London: Springer; 2013. pp. 173-193\n'},{id:"B30",body:'\nLevermore R. Evaluating sport-for-development: Approaches and critical issues. Progress in Development Studies. 2011;11(4):339-353\n'},{id:"B31",body:'\nLevermore R, Beacom A. In: Wagg S, Andrews D, editors. Sport and International Development. Basingstoke, UK: Palgrave Macmillan; 2009\n'},{id:"B32",body:'\nArellano A, Halsall T, Forneris T, Gaudet C. Results of a utilization-focused evaluation of a right to play program for indigenous youth. Evaluation and Program Planning. 2018;66:156-164\n'},{id:"B33",body:'\nSimard S. Le développement positif des jeunes en contexte sportif parascolaire: évaluation du programme d’intervention psychosociale Bien dans mes Baskets. Montreal: Universite de Montréal; 2013\n'},{id:"B34",body:'\nCoalter F. Sport-in-Development: A Monitoring and Evaluation Manual. The International Platform on Sport & Development. London: UK Sport; 2008. Available from: http://www.sportni.net/sportni/wp-content/uploads/2013/03/Sport_in_Development_A_monitoring_and_Evaluation_Manual.pdf [Accessed June 2019]\n'},{id:"B35",body:'\nLyras A, Welty-Peachey J. Integrating sport-for-development theory and praxis. Sport Management Review. 2011;14(4):311-326\n'},{id:"B36",body:'\nPeachey JW, Borland J, Lobpries J, Cohen A. Managing impact: Leveraging sacred spaces and community celebration to maximize social capital at a sport-for-development event. Sport Management Review. 2015;18(1):86-98\n'},{id:"B37",body:'\nSchulenkorf N. Managing sport-for-development: Reflections and outlook. Sport Management Review. 2017;20(3):243-251\n'},{id:"B38",body:'\nSvensson P, Woods H. A systematic overview of sport for development and peace organisations. Journal of Sport for Development. 2017;5(9):36-48\n'},{id:"B39",body:'\nJones GJ, Edwards MB, Bocarro JN, Bunds KS, Smith JW. An integrative review of sport-based youth development literature. Sport in Society. 2017;20(1):161-179\n'},{id:"B40",body:'\nGreimas AJ. Du sens II. Paris: Seuil; 1983. p. 245\n'},{id:"B41",body:'\nGadais T, Décarpentrie L, Ayoub M-B, Bardocz-Bencsik M, Rouzaut M, Dalcourt-Malenfant S, editors. Understanding Sport for Development and Peace Organisation and their Context from a Distance by Using Actantial Model: The Case of Bel Avenir (Madagascar). AIESEP. NY, USA: Adelphi University; 2019\n'},{id:"B42",body:'\nDécarpentrie L. Les effets de la participation à des activités extrascolaires en contexte extrême de développement: le cas de jeunes à Madagascar. Montréal: Université du Québec à Montréal; 2019. p. 79\n'},{id:"B43",body:'\nFalcão WR, Bloom GA, Bennie A. Coaches’ experiences learning and applying the content of a humanistic coaching workshop in youth sport settings. International Sport Coaching Journal. 2017;4:279-290\n'},{id:"B44",body:'\nGadais T, Bardocz-Bencsik M, Falcão WR. Analyzing a SDP program’s logical model with key actors’ perceptions: The case of Pour 3 Points organization in Montreal. in press\n'},{id:"B45",body:'\nHills S, Velásquez AG, Walker M. Sport as an analogy to teach life skills and redefine moral values: A case study of the ‘seedbeds of peace’ sport-for-development programme in Medellin, Colombia. Journal of Sport for Development. 2018;6(11):19-31\n'},{id:"B46",body:'\nCoalter F. Sport-in-Development: Accountability or Development?. Sport and International Development. UK: Palgrave Macmillan; 2009. pp. 55-75\n'},{id:"B47",body:'\nArnaud L. Sport as a cultural system: Sports policies and (new) ethnicities in Lyon and Birmingham. International Journal of Urban and Regional Research. 2002;26(3):571-587\n'},{id:"B48",body:'\nBergsgard NA, Houlihan B, Mangset P, Nødland SI, Rommetvedt H. Sport Policy: A Comparative Analysis of Stability and Change. Oxford: Elsevier; 2009\n'},{id:"B49",body:'\nWalker M, Hills S, Heere B. Evaluating a socially responsible employment program: Beneficiary impacts and stakeholder perceptions. Journal of Business Ethics. 2015;143(1):53-70\n'},{id:"B50",body:'\nWalker Research Group. The role of boxing in development. 2017. Available from: http://www.abae.co.uk/aba/index. cfm/news/new-research-in-hackneyand-liverpool-details-how-and-whyboxing-combats-anti-social-behaviourin-deprived-communities/ [Accessed June 2019]\n'},{id:"B51",body:'\nDanish SJ, Nellen VC. New roles for sport psychologists: Teaching life skills through sport to at-risk youth. Quest. 1997;49(1):100-113\n'},{id:"B52",body:'\nHeere B, James JD. Sports teams and their communities: Examining the influence of external group identities on team identity. Journal of Sport Management. 2007;21(3):319-337\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Tegwen Gadais",address:"gadais.tegwen@uqam.ca",affiliation:'
Université du Québec à Montréal (UQAM), Montréal, Canada
'}],corrections:null},book:{id:"9158",title:"Sports Science and Human Health",subtitle:"Different Approaches",fullTitle:"Sports Science and Human Health - Different Approaches",slug:"sports-science-and-human-health-different-approaches",publishedDate:"December 23rd 2020",bookSignature:"Daniel Almeida Marinho, Henrique P. Neiva, Christopher P. Johnson and Nawaz Mohamudally",coverURL:"https://cdn.intechopen.com/books/images_new/9158.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"177359",title:"Dr.",name:"Daniel Almeida",middleName:"Almeida",surname:"Marinho",slug:"daniel-almeida-marinho",fullName:"Daniel Almeida Marinho"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},profile:{item:{id:"171948",title:"BSc.",name:"Hevertton",middleName:null,surname:"Barbosa",email:"kikuchi@exodus.eti.br",fullName:"Hevertton Barbosa",slug:"hevertton-barbosa",position:null,biography:null,institutionString:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",totalCites:0,totalChapterViews:"0",outsideEditionCount:0,totalAuthoredChapters:"1",totalEditedBooks:"0",personalWebsiteURL:null,twitterURL:null,linkedinURL:null,institution:null},booksEdited:[],chaptersAuthored:[{title:"A Simple Fuzzy System Applied to Predict Default Rate",slug:"a-simple-fuzzy-system-applied-to-predict-default-rate",abstract:null,signatures:"Fábio M. Soares, Olavo S. Rocha Neto and Hevertton H. K. Barbosa",authors:[{id:"104491",title:"MSc.",name:"Fabio",surname:"Soares",fullName:"Fabio Soares",slug:"fabio-soares",email:"fabio@exodus.eti.br"},{id:"171947",title:"BSc.",name:"Olavo",surname:"Rocha",fullName:"Olavo Rocha",slug:"olavo-rocha",email:"olavo@exodus.eti.br"},{id:"171948",title:"BSc.",name:"Hevertton",surname:"Barbosa",fullName:"Hevertton Barbosa",slug:"hevertton-barbosa",email:"kikuchi@exodus.eti.br"}],book:{title:"Fuzzy Logic",slug:"fuzzy-logic-tool-for-getting-accurate-solutions",productType:{id:"1",title:"Edited Volume"}}}],collaborators:[{id:"107166",title:"Dr.",name:"Toshihisa",surname:"Sato",slug:"toshihisa-sato",fullName:"Toshihisa Sato",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Institute of Advanced Industrial Science and Technology",institutionURL:null,country:{name:"Japan"}}},{id:"114149",title:"Dr.",name:"Angelo",surname:"Rezek",slug:"angelo-rezek",fullName:"Angelo Rezek",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Federal University of Itajubá",institutionURL:null,country:{name:"Brazil"}}},{id:"114169",title:"Prof.",name:"Carlos",surname:"A. M. Pinheiro",slug:"carlos-a.-m.-pinheiro",fullName:"Carlos A. M. Pinheiro",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"171506",title:"Dr.",name:"Salman",surname:"Mohagheghi",slug:"salman-mohagheghi",fullName:"Salman Mohagheghi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Colorado School of Mines",institutionURL:null,country:{name:"United States of America"}}},{id:"171674",title:"MSc.",name:"Tony",surname:"Darido",slug:"tony-darido",fullName:"Tony Darido",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"171675",title:"Dr.",name:"Valberto",surname:"Silva",slug:"valberto-silva",fullName:"Valberto Silva",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"171676",title:"Dr.",name:"Wanderson",surname:"Assis",slug:"wanderson-assis",fullName:"Wanderson Assis",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"171677",title:"BSc.",name:"Otavio",surname:"Vicentini",slug:"otavio-vicentini",fullName:"Otavio Vicentini",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"171678",title:"MSc.",name:"Rafael",surname:"Correa",slug:"rafael-correa",fullName:"Rafael Correa",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"171779",title:"Associate Prof.",name:"Salman",surname:"Hameed",slug:"salman-hameed",fullName:"Salman Hameed",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Aligarh Muslim University",institutionURL:null,country:{name:"India"}}}]},generic:{page:{slug:"our-story",title:"Our story",intro:"
The company was founded in Vienna in 2004 by Alex Lazinica and Vedran Kordic, two PhD students researching robotics. While completing our PhDs, we found it difficult to access the research we needed. So, we decided to create a new Open Access publisher. A better one, where researchers like us could find the information they needed easily. The result is IntechOpen, an Open Access publisher that puts the academic needs of the researchers before the business interests of publishers.
",metaTitle:"Our story",metaDescription:"The company was founded in Vienna in 2004 by Alex Lazinica and Vedran Kordic, two PhD students researching robotics. While completing our PhDs, we found it difficult to access the research we needed. So, we decided to create a new Open Access publisher. A better one, where researchers like us could find the information they needed easily. The result is IntechOpen, an Open Access publisher that puts the academic needs of the researchers before the business interests of publishers.",metaKeywords:null,canonicalURL:"/page/our-story",contentRaw:'[{"type":"htmlEditorComponent","content":"
We started by publishing journals and books from the fields of science we were most familiar with - AI, robotics, manufacturing and operations research. Through our growing network of institutions and authors, we soon expanded into related fields like environmental engineering, nanotechnology, computer science, renewable energy and electrical engineering, Today, we are the world’s largest Open Access publisher of scientific research, with over 4,200 books and 54,000 scientific works including peer-reviewed content from more than 116,000 scientists spanning 161 countries. Our authors range from globally-renowned Nobel Prize winners to up-and-coming researchers at the cutting edge of scientific discovery.
\\n\\n
In the same year that IntechOpen was founded, we launched what was at the time the first ever Open Access, peer-reviewed journal in its field: the International Journal of Advanced Robotic Systems (IJARS).
\\n\\n
The IntechOpen timeline
\\n\\n
2004
\\n\\n
\\n\\t
Intech Open is founded in Vienna, Austria, by Alex Lazinica and Vedran Kordic, two PhD students, and their first Open Access journals and books are published.
\\n\\t
Alex and Vedran launch the first Open Access, peer-reviewed robotics journal and IntechOpen’s flagship publication, the International Journal of Advanced Robotic Systems (IJARS).
\\n
\\n\\n
2005
\\n\\n
\\n\\t
IntechOpen publishes its first Open Access book: Cutting Edge Robotics.
\\n
\\n\\n
2006
\\n\\n
\\n\\t
IntechOpen publishes a special issue of IJARS, featuring contributions from NASA scientists regarding the Mars Exploration Rover missions.
\\n
\\n\\n
2008
\\n\\n
\\n\\t
Downloads milestone: 200,000 downloads reached
\\n
\\n\\n
2009
\\n\\n
\\n\\t
Publishing milestone: the first 100 Open Access STM books are published
\\n
\\n\\n
2010
\\n\\n
\\n\\t
Downloads milestone: one million downloads reached
\\n\\t
IntechOpen expands its book publishing into a new field: medicine.
\\n
\\n\\n
2011
\\n\\n
\\n\\t
Publishing milestone: More than five million downloads reached
\\n\\t
IntechOpen publishes 1996 Nobel Prize in Chemistry winner Harold W. Kroto’s “Strategies to Successfully Cross-Link Carbon Nanotubes”. Find it here.
\\n\\t
IntechOpen and TBI collaborate on a project to explore the changing needs of researchers and the evolving ways that they discover, publish and exchange information. The result is the survey “Author Attitudes Towards Open Access Publishing: A Market Research Program”.
\\n\\t
IntechOpen hosts SHOW - Share Open Access Worldwide; a series of lectures, debates, round-tables and events to bring people together in discussion of open source principles, intellectual property, content licensing innovations, remixed and shared culture and free knowledge.
\\n
\\n\\n
2012
\\n\\n
\\n\\t
Publishing milestone: 10 million downloads reached
\\n\\t
IntechOpen holds Interact2012, a free series of workshops held by figureheads of the scientific community including Professor Hiroshi Ishiguro, director of the Intelligent Robotics Laboratory, who took the audience through some of the most impressive human-robot interactions observed in his lab.
\\n
\\n\\n
2013
\\n\\n
\\n\\t
IntechOpen joins the Committee on Publication Ethics (COPE) as part of a commitment to guaranteeing the highest standards of publishing.
\\n
\\n\\n
2014
\\n\\n
\\n\\t
IntechOpen turns 10, with more than 30 million downloads to date.
\\n\\t
IntechOpen appoints its first Regional Representatives - members of the team situated around the world dedicated to increasing the visibility of our authors’ published work within their local scientific communities.
\\n
\\n\\n
2015
\\n\\n
\\n\\t
Downloads milestone: More than 70 million downloads reached, more than doubling since the previous year.
\\n\\t
Publishing milestone: IntechOpen publishes its 2,500th book and 40,000th Open Access chapter, reaching 20,000 citations in Thomson Reuters ISI Web of Science.
\\n\\t
40 IntechOpen authors are included in the top one per cent of the world’s most-cited researchers.
\\n\\t
Thomson Reuters’ ISI Web of Science Book Citation Index begins indexing IntechOpen’s books in its database.
\\n
\\n\\n
2016
\\n\\n
\\n\\t
IntechOpen is identified as a world leader in Simba Information’s Open Access Book Publishing 2016-2020 report and forecast. IntechOpen came in as the world’s largest Open Access book publisher by title count.
\\n
\\n\\n
2017
\\n\\n
\\n\\t
Downloads milestone: IntechOpen reaches more than 100 million downloads
\\n\\t
Publishing milestone: IntechOpen publishes its 3,000th Open Access book, making it the largest Open Access book collection in the world
We started by publishing journals and books from the fields of science we were most familiar with - AI, robotics, manufacturing and operations research. Through our growing network of institutions and authors, we soon expanded into related fields like environmental engineering, nanotechnology, computer science, renewable energy and electrical engineering, Today, we are the world’s largest Open Access publisher of scientific research, with over 4,200 books and 54,000 scientific works including peer-reviewed content from more than 116,000 scientists spanning 161 countries. Our authors range from globally-renowned Nobel Prize winners to up-and-coming researchers at the cutting edge of scientific discovery.
\n\n
In the same year that IntechOpen was founded, we launched what was at the time the first ever Open Access, peer-reviewed journal in its field: the International Journal of Advanced Robotic Systems (IJARS).
\n\n
The IntechOpen timeline
\n\n
2004
\n\n
\n\t
Intech Open is founded in Vienna, Austria, by Alex Lazinica and Vedran Kordic, two PhD students, and their first Open Access journals and books are published.
\n\t
Alex and Vedran launch the first Open Access, peer-reviewed robotics journal and IntechOpen’s flagship publication, the International Journal of Advanced Robotic Systems (IJARS).
\n
\n\n
2005
\n\n
\n\t
IntechOpen publishes its first Open Access book: Cutting Edge Robotics.
\n
\n\n
2006
\n\n
\n\t
IntechOpen publishes a special issue of IJARS, featuring contributions from NASA scientists regarding the Mars Exploration Rover missions.
\n
\n\n
2008
\n\n
\n\t
Downloads milestone: 200,000 downloads reached
\n
\n\n
2009
\n\n
\n\t
Publishing milestone: the first 100 Open Access STM books are published
\n
\n\n
2010
\n\n
\n\t
Downloads milestone: one million downloads reached
\n\t
IntechOpen expands its book publishing into a new field: medicine.
\n
\n\n
2011
\n\n
\n\t
Publishing milestone: More than five million downloads reached
\n\t
IntechOpen publishes 1996 Nobel Prize in Chemistry winner Harold W. Kroto’s “Strategies to Successfully Cross-Link Carbon Nanotubes”. Find it here.
\n\t
IntechOpen and TBI collaborate on a project to explore the changing needs of researchers and the evolving ways that they discover, publish and exchange information. The result is the survey “Author Attitudes Towards Open Access Publishing: A Market Research Program”.
\n\t
IntechOpen hosts SHOW - Share Open Access Worldwide; a series of lectures, debates, round-tables and events to bring people together in discussion of open source principles, intellectual property, content licensing innovations, remixed and shared culture and free knowledge.
\n
\n\n
2012
\n\n
\n\t
Publishing milestone: 10 million downloads reached
\n\t
IntechOpen holds Interact2012, a free series of workshops held by figureheads of the scientific community including Professor Hiroshi Ishiguro, director of the Intelligent Robotics Laboratory, who took the audience through some of the most impressive human-robot interactions observed in his lab.
\n
\n\n
2013
\n\n
\n\t
IntechOpen joins the Committee on Publication Ethics (COPE) as part of a commitment to guaranteeing the highest standards of publishing.
\n
\n\n
2014
\n\n
\n\t
IntechOpen turns 10, with more than 30 million downloads to date.
\n\t
IntechOpen appoints its first Regional Representatives - members of the team situated around the world dedicated to increasing the visibility of our authors’ published work within their local scientific communities.
\n
\n\n
2015
\n\n
\n\t
Downloads milestone: More than 70 million downloads reached, more than doubling since the previous year.
\n\t
Publishing milestone: IntechOpen publishes its 2,500th book and 40,000th Open Access chapter, reaching 20,000 citations in Thomson Reuters ISI Web of Science.
\n\t
40 IntechOpen authors are included in the top one per cent of the world’s most-cited researchers.
\n\t
Thomson Reuters’ ISI Web of Science Book Citation Index begins indexing IntechOpen’s books in its database.
\n
\n\n
2016
\n\n
\n\t
IntechOpen is identified as a world leader in Simba Information’s Open Access Book Publishing 2016-2020 report and forecast. IntechOpen came in as the world’s largest Open Access book publisher by title count.
\n
\n\n
2017
\n\n
\n\t
Downloads milestone: IntechOpen reaches more than 100 million downloads
\n\t
Publishing milestone: IntechOpen publishes its 3,000th Open Access book, making it the largest Open Access book collection in the world
\n
\n"}]},successStories:{items:[]},authorsAndEditors:{filterParams:{sort:"featured,name"},profiles:[{id:"6700",title:"Dr.",name:"Abbass A.",middleName:null,surname:"Hashim",slug:"abbass-a.-hashim",fullName:"Abbass A. Hashim",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/6700/images/1864_n.jpg",biography:"Currently I am carrying out research in several areas of interest, mainly covering work on chemical and bio-sensors, semiconductor thin film device fabrication and characterisation.\nAt the moment I have very strong interest in radiation environmental pollution and bacteriology treatment. The teams of researchers are working very hard to bring novel results in this field. I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. I have served as the editor for many books, been a member of the editorial board in science journals, have published many papers and hold many patents.",institutionString:null,institution:{name:"Sheffield Hallam University",country:{name:"United Kingdom"}}},{id:"54525",title:"Prof.",name:"Abdul Latif",middleName:null,surname:"Ahmad",slug:"abdul-latif-ahmad",fullName:"Abdul Latif Ahmad",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"20567",title:"Prof.",name:"Ado",middleName:null,surname:"Jorio",slug:"ado-jorio",fullName:"Ado Jorio",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidade Federal de Minas Gerais",country:{name:"Brazil"}}},{id:"47940",title:"Dr.",name:"Alberto",middleName:null,surname:"Mantovani",slug:"alberto-mantovani",fullName:"Alberto Mantovani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12392/images/7282_n.png",biography:"Alex Lazinica is the founder and CEO of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his PhD studies in Robotics at the Vienna University of Technology. Here he worked as a robotic researcher with the university's Intelligent Manufacturing Systems Group as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and most importantly he co-founded and built the International Journal of Advanced Robotic Systems- world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career, since it was a pathway to founding IntechOpen - Open Access publisher focused on addressing academic researchers needs. Alex is a personification of IntechOpen key values being trusted, open and entrepreneurial. Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\r\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. He is an expert in structural, absorptive, catalytic and photocatalytic properties, in structural organization and dynamic features of ionic liquids, in magnetic interactions between paramagnetic centers. The author or co-author of 3 books, over 200 articles and reviews in scientific journals and books. He is an actual member of the International EPR/ESR Society, European Society on Quantum Solar Energy Conversion, Moscow House of Scientists, of the Board of Moscow Physical Society.",institutionString:null,institution:{name:"Semenov Institute of Chemical Physics",country:{name:"Russia"}}},{id:"62389",title:"PhD.",name:"Ali Demir",middleName:null,surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62389/images/3413_n.jpg",biography:"Dr. Ali Demir Sezer has a Ph.D. from Pharmaceutical Biotechnology at the Faculty of Pharmacy, University of Marmara (Turkey). He is the member of many Pharmaceutical Associations and acts as a reviewer of scientific journals and European projects under different research areas such as: drug delivery systems, nanotechnology and pharmaceutical biotechnology. Dr. Sezer is the author of many scientific publications in peer-reviewed journals and poster communications. Focus of his research activity is drug delivery, physico-chemical characterization and biological evaluation of biopolymers micro and nanoparticles as modified drug delivery system, and colloidal drug carriers (liposomes, nanoparticles etc.).",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"61051",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"100762",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"St David's Medical Center",country:{name:"United States of America"}}},{id:"107416",title:"Dr.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Texas Cardiac Arrhythmia",country:{name:"United States of America"}}},{id:"64434",title:"Dr.",name:"Angkoon",middleName:null,surname:"Phinyomark",slug:"angkoon-phinyomark",fullName:"Angkoon Phinyomark",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/64434/images/2619_n.jpg",biography:"My name is Angkoon Phinyomark. I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. I had been a visiting research student at Faculty of Computer Science, University of Murcia, Murcia, Spain for three months.\n\nI have published over 40 papers during 5 years in refereed journals, books, and conference proceedings in the areas of electro-physiological signals processing and classification, notably EMG and EOG signals, fractal analysis, wavelet analysis, texture analysis, feature extraction and machine learning algorithms, and assistive and rehabilitative devices. I have several computer programming language certificates, i.e. Sun Certified Programmer for the Java 2 Platform 1.4 (SCJP), Microsoft Certified Professional Developer, Web Developer (MCPD), Microsoft Certified Technology Specialist, .NET Framework 2.0 Web (MCTS). I am a Reviewer for several refereed journals and international conferences, such as IEEE Transactions on Biomedical Engineering, IEEE Transactions on Industrial Electronics, Optic Letters, Measurement Science Review, and also a member of the International Advisory Committee for 2012 IEEE Business Engineering and Industrial Applications and 2012 IEEE Symposium on Business, Engineering and Industrial Applications.",institutionString:null,institution:{name:"Joseph Fourier University",country:{name:"France"}}},{id:"55578",title:"Dr.",name:"Antonio",middleName:null,surname:"Jurado-Navas",slug:"antonio-jurado-navas",fullName:"Antonio Jurado-Navas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/55578/images/4574_n.png",biography:"Antonio Jurado-Navas received the M.S. degree (2002) and the Ph.D. degree (2009) in Telecommunication Engineering, both from the University of Málaga (Spain). He first worked as a consultant at Vodafone-Spain. From 2004 to 2011, he was a Research Assistant with the Communications Engineering Department at the University of Málaga. In 2011, he became an Assistant Professor in the same department. From 2012 to 2015, he was with Ericsson Spain, where he was working on geo-location\ntools for third generation mobile networks. Since 2015, he is a Marie-Curie fellow at the Denmark Technical University. His current research interests include the areas of mobile communication systems and channel modeling in addition to atmospheric optical communications, adaptive optics and statistics",institutionString:null,institution:{name:"University of Malaga",country:{name:"Spain"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:5699},{group:"region",caption:"Middle and South America",value:2,count:5172},{group:"region",caption:"Africa",value:3,count:1689},{group:"region",caption:"Asia",value:4,count:10244},{group:"region",caption:"Australia and Oceania",value:5,count:888},{group:"region",caption:"Europe",value:6,count:15650}],offset:12,limit:12,total:117315},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{sort:"dateendthirdsteppublish"},books:[],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:9},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:15},{group:"topic",caption:"Business, Management and Economics",value:7,count:2},{group:"topic",caption:"Chemistry",value:8,count:6},{group:"topic",caption:"Computer and Information Science",value:9,count:10},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:4},{group:"topic",caption:"Engineering",value:11,count:15},{group:"topic",caption:"Environmental Sciences",value:12,count:2},{group:"topic",caption:"Immunology and Microbiology",value:13,count:4},{group:"topic",caption:"Materials Science",value:14,count:4},{group:"topic",caption:"Mathematics",value:15,count:1},{group:"topic",caption:"Medicine",value:16,count:56},{group:"topic",caption:"Neuroscience",value:18,count:1},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:5},{group:"topic",caption:"Physics",value:20,count:2},{group:"topic",caption:"Psychology",value:21,count:3},{group:"topic",caption:"Robotics",value:22,count:1},{group:"topic",caption:"Social Sciences",value:23,count:3},{group:"topic",caption:"Technology",value:24,count:1},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:2}],offset:0,limit:12,total:null},popularBooks:{featuredBooks:[{type:"book",id:"7802",title:"Modern Slavery and Human Trafficking",subtitle:null,isOpenForSubmission:!1,hash:"587a0b7fb765f31cc98de33c6c07c2e0",slug:"modern-slavery-and-human-trafficking",bookSignature:"Jane Reeves",coverURL:"https://cdn.intechopen.com/books/images_new/7802.jpg",editors:[{id:"211328",title:"Prof.",name:"Jane",middleName:null,surname:"Reeves",slug:"jane-reeves",fullName:"Jane Reeves"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8545",title:"Animal Reproduction in Veterinary Medicine",subtitle:null,isOpenForSubmission:!1,hash:"13aaddf5fdbbc78387e77a7da2388bf6",slug:"animal-reproduction-in-veterinary-medicine",bookSignature:"Faruk Aral, Rita Payan-Carreira and Miguel Quaresma",coverURL:"https://cdn.intechopen.com/books/images_new/8545.jpg",editors:[{id:"25600",title:"Prof.",name:"Faruk",middleName:null,surname:"Aral",slug:"faruk-aral",fullName:"Faruk Aral"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9961",title:"Data Mining",subtitle:"Methods, Applications and Systems",isOpenForSubmission:!1,hash:"ed79fb6364f2caf464079f94a0387146",slug:"data-mining-methods-applications-and-systems",bookSignature:"Derya Birant",coverURL:"https://cdn.intechopen.com/books/images_new/9961.jpg",editors:[{id:"15609",title:"Dr.",name:"Derya",middleName:null,surname:"Birant",slug:"derya-birant",fullName:"Derya Birant"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9157",title:"Neurodegenerative Diseases",subtitle:"Molecular Mechanisms and Current Therapeutic Approaches",isOpenForSubmission:!1,hash:"bc8be577966ef88735677d7e1e92ed28",slug:"neurodegenerative-diseases-molecular-mechanisms-and-current-therapeutic-approaches",bookSignature:"Nagehan Ersoy Tunalı",coverURL:"https://cdn.intechopen.com/books/images_new/9157.jpg",editors:[{id:"82778",title:"Ph.D.",name:"Nagehan",middleName:null,surname:"Ersoy Tunalı",slug:"nagehan-ersoy-tunali",fullName:"Nagehan Ersoy Tunalı"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8686",title:"Direct Torque Control Strategies of Electrical Machines",subtitle:null,isOpenForSubmission:!1,hash:"b6ad22b14db2b8450228545d3d4f6b1a",slug:"direct-torque-control-strategies-of-electrical-machines",bookSignature:"Fatma Ben Salem",coverURL:"https://cdn.intechopen.com/books/images_new/8686.jpg",editors:[{id:"295623",title:"Associate Prof.",name:"Fatma",middleName:null,surname:"Ben Salem",slug:"fatma-ben-salem",fullName:"Fatma Ben Salem"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7434",title:"Molecular Biotechnology",subtitle:null,isOpenForSubmission:!1,hash:"eceede809920e1ec7ecadd4691ede2ec",slug:"molecular-biotechnology",bookSignature:"Sergey Sedykh",coverURL:"https://cdn.intechopen.com/books/images_new/7434.jpg",editors:[{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",slug:"sergey-sedykh",fullName:"Sergey Sedykh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9839",title:"Outdoor Recreation",subtitle:"Physiological and Psychological Effects on Health",isOpenForSubmission:!1,hash:"5f5a0d64267e32567daffa5b0c6a6972",slug:"outdoor-recreation-physiological-and-psychological-effects-on-health",bookSignature:"Hilde G. Nielsen",coverURL:"https://cdn.intechopen.com/books/images_new/9839.jpg",editors:[{id:"158692",title:"Ph.D.",name:"Hilde G.",middleName:null,surname:"Nielsen",slug:"hilde-g.-nielsen",fullName:"Hilde G. Nielsen"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9208",title:"Welding",subtitle:"Modern Topics",isOpenForSubmission:!1,hash:"7d6be076ccf3a3f8bd2ca52d86d4506b",slug:"welding-modern-topics",bookSignature:"Sadek Crisóstomo Absi Alfaro, Wojciech Borek and Błażej Tomiczek",coverURL:"https://cdn.intechopen.com/books/images_new/9208.jpg",editors:[{id:"65292",title:"Prof.",name:"Sadek Crisostomo Absi",middleName:"C. Absi",surname:"Alfaro",slug:"sadek-crisostomo-absi-alfaro",fullName:"Sadek Crisostomo Absi Alfaro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9139",title:"Topics in Primary Care Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ea774a4d4c1179da92a782e0ae9cde92",slug:"topics-in-primary-care-medicine",bookSignature:"Thomas F. Heston",coverURL:"https://cdn.intechopen.com/books/images_new/9139.jpg",editors:[{id:"217926",title:"Dr.",name:"Thomas F.",middleName:null,surname:"Heston",slug:"thomas-f.-heston",fullName:"Thomas F. Heston"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9343",title:"Trace Metals in the Environment",subtitle:"New Approaches and Recent Advances",isOpenForSubmission:!1,hash:"ae07e345bc2ce1ebbda9f70c5cd12141",slug:"trace-metals-in-the-environment-new-approaches-and-recent-advances",bookSignature:"Mario Alfonso Murillo-Tovar, Hugo Saldarriaga-Noreña and Agnieszka Saeid",coverURL:"https://cdn.intechopen.com/books/images_new/9343.jpg",editors:[{id:"255959",title:"Dr.",name:"Mario Alfonso",middleName:null,surname:"Murillo-Tovar",slug:"mario-alfonso-murillo-tovar",fullName:"Mario Alfonso Murillo-Tovar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8697",title:"Virtual Reality and Its Application in Education",subtitle:null,isOpenForSubmission:!1,hash:"ee01b5e387ba0062c6b0d1e9227bda05",slug:"virtual-reality-and-its-application-in-education",bookSignature:"Dragan Cvetković",coverURL:"https://cdn.intechopen.com/books/images_new/8697.jpg",editors:[{id:"101330",title:"Dr.",name:"Dragan",middleName:"Mladen",surname:"Cvetković",slug:"dragan-cvetkovic",fullName:"Dragan Cvetković"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7831",title:"Sustainability in Urban Planning and Design",subtitle:null,isOpenForSubmission:!1,hash:"c924420492c8c2c9751e178d025f4066",slug:"sustainability-in-urban-planning-and-design",bookSignature:"Amjad Almusaed, Asaad Almssad and Linh Truong - Hong",coverURL:"https://cdn.intechopen.com/books/images_new/7831.jpg",editors:[{id:"110471",title:"Dr.",name:"Amjad",middleName:"Zaki",surname:"Almusaed",slug:"amjad-almusaed",fullName:"Amjad Almusaed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:5145},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"9208",title:"Welding",subtitle:"Modern Topics",isOpenForSubmission:!1,hash:"7d6be076ccf3a3f8bd2ca52d86d4506b",slug:"welding-modern-topics",bookSignature:"Sadek Crisóstomo Absi Alfaro, Wojciech Borek and Błażej Tomiczek",coverURL:"https://cdn.intechopen.com/books/images_new/9208.jpg",editors:[{id:"65292",title:"Prof.",name:"Sadek Crisostomo Absi",middleName:"C. Absi",surname:"Alfaro",slug:"sadek-crisostomo-absi-alfaro",fullName:"Sadek Crisostomo Absi Alfaro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9139",title:"Topics in Primary Care Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ea774a4d4c1179da92a782e0ae9cde92",slug:"topics-in-primary-care-medicine",bookSignature:"Thomas F. Heston",coverURL:"https://cdn.intechopen.com/books/images_new/9139.jpg",editors:[{id:"217926",title:"Dr.",name:"Thomas F.",middleName:null,surname:"Heston",slug:"thomas-f.-heston",fullName:"Thomas F. Heston"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8697",title:"Virtual Reality and Its Application in Education",subtitle:null,isOpenForSubmission:!1,hash:"ee01b5e387ba0062c6b0d1e9227bda05",slug:"virtual-reality-and-its-application-in-education",bookSignature:"Dragan Cvetković",coverURL:"https://cdn.intechopen.com/books/images_new/8697.jpg",editors:[{id:"101330",title:"Dr.",name:"Dragan",middleName:"Mladen",surname:"Cvetković",slug:"dragan-cvetkovic",fullName:"Dragan Cvetković"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9343",title:"Trace Metals in the Environment",subtitle:"New Approaches and Recent Advances",isOpenForSubmission:!1,hash:"ae07e345bc2ce1ebbda9f70c5cd12141",slug:"trace-metals-in-the-environment-new-approaches-and-recent-advances",bookSignature:"Mario Alfonso Murillo-Tovar, Hugo Saldarriaga-Noreña and Agnieszka Saeid",coverURL:"https://cdn.intechopen.com/books/images_new/9343.jpg",editors:[{id:"255959",title:"Dr.",name:"Mario Alfonso",middleName:null,surname:"Murillo-Tovar",slug:"mario-alfonso-murillo-tovar",fullName:"Mario Alfonso Murillo-Tovar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9785",title:"Endometriosis",subtitle:null,isOpenForSubmission:!1,hash:"f457ca61f29cf7e8bc191732c50bb0ce",slug:"endometriosis",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7831",title:"Sustainability in Urban Planning and Design",subtitle:null,isOpenForSubmission:!1,hash:"c924420492c8c2c9751e178d025f4066",slug:"sustainability-in-urban-planning-and-design",bookSignature:"Amjad Almusaed, Asaad Almssad and Linh Truong - Hong",coverURL:"https://cdn.intechopen.com/books/images_new/7831.jpg",editors:[{id:"110471",title:"Dr.",name:"Amjad",middleName:"Zaki",surname:"Almusaed",slug:"amjad-almusaed",fullName:"Amjad Almusaed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9376",title:"Contemporary Developments and Perspectives in International Health Security",subtitle:"Volume 1",isOpenForSubmission:!1,hash:"b9a00b84cd04aae458fb1d6c65795601",slug:"contemporary-developments-and-perspectives-in-international-health-security-volume-1",bookSignature:"Stanislaw P. Stawicki, Michael S. Firstenberg, Sagar C. Galwankar, Ricardo Izurieta and Thomas Papadimos",coverURL:"https://cdn.intechopen.com/books/images_new/9376.jpg",editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",middleName:null,surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7769",title:"Medical Isotopes",subtitle:null,isOpenForSubmission:!1,hash:"f8d3c5a6c9a42398e56b4e82264753f7",slug:"medical-isotopes",bookSignature:"Syed Ali Raza Naqvi and Muhammad Babar Imrani",coverURL:"https://cdn.intechopen.com/books/images_new/7769.jpg",editors:[{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9279",title:"Concepts, Applications and Emerging Opportunities in Industrial Engineering",subtitle:null,isOpenForSubmission:!1,hash:"9bfa87f9b627a5468b7c1e30b0eea07a",slug:"concepts-applications-and-emerging-opportunities-in-industrial-engineering",bookSignature:"Gary Moynihan",coverURL:"https://cdn.intechopen.com/books/images_new/9279.jpg",editors:[{id:"16974",title:"Dr.",name:"Gary",middleName:null,surname:"Moynihan",slug:"gary-moynihan",fullName:"Gary Moynihan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7807",title:"A Closer Look at Organizational Culture in Action",subtitle:null,isOpenForSubmission:!1,hash:"05c608b9271cc2bc711f4b28748b247b",slug:"a-closer-look-at-organizational-culture-in-action",bookSignature:"Süleyman Davut Göker",coverURL:"https://cdn.intechopen.com/books/images_new/7807.jpg",editors:[{id:"190035",title:"Associate Prof.",name:"Süleyman Davut",middleName:null,surname:"Göker",slug:"suleyman-davut-goker",fullName:"Süleyman Davut Göker"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"7434",title:"Molecular Biotechnology",subtitle:null,isOpenForSubmission:!1,hash:"eceede809920e1ec7ecadd4691ede2ec",slug:"molecular-biotechnology",bookSignature:"Sergey Sedykh",coverURL:"https://cdn.intechopen.com/books/images_new/7434.jpg",editedByType:"Edited by",editors:[{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",slug:"sergey-sedykh",fullName:"Sergey Sedykh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8545",title:"Animal Reproduction in Veterinary Medicine",subtitle:null,isOpenForSubmission:!1,hash:"13aaddf5fdbbc78387e77a7da2388bf6",slug:"animal-reproduction-in-veterinary-medicine",bookSignature:"Faruk Aral, Rita Payan-Carreira and Miguel Quaresma",coverURL:"https://cdn.intechopen.com/books/images_new/8545.jpg",editedByType:"Edited by",editors:[{id:"25600",title:"Prof.",name:"Faruk",middleName:null,surname:"Aral",slug:"faruk-aral",fullName:"Faruk Aral"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9569",title:"Methods in Molecular Medicine",subtitle:null,isOpenForSubmission:!1,hash:"691d3f3c4ac25a8093414e9b270d2843",slug:"methods-in-molecular-medicine",bookSignature:"Yusuf Tutar",coverURL:"https://cdn.intechopen.com/books/images_new/9569.jpg",editedByType:"Edited by",editors:[{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9839",title:"Outdoor Recreation",subtitle:"Physiological and Psychological Effects on Health",isOpenForSubmission:!1,hash:"5f5a0d64267e32567daffa5b0c6a6972",slug:"outdoor-recreation-physiological-and-psychological-effects-on-health",bookSignature:"Hilde G. Nielsen",coverURL:"https://cdn.intechopen.com/books/images_new/9839.jpg",editedByType:"Edited by",editors:[{id:"158692",title:"Ph.D.",name:"Hilde G.",middleName:null,surname:"Nielsen",slug:"hilde-g.-nielsen",fullName:"Hilde G. Nielsen"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7802",title:"Modern Slavery and Human Trafficking",subtitle:null,isOpenForSubmission:!1,hash:"587a0b7fb765f31cc98de33c6c07c2e0",slug:"modern-slavery-and-human-trafficking",bookSignature:"Jane Reeves",coverURL:"https://cdn.intechopen.com/books/images_new/7802.jpg",editedByType:"Edited by",editors:[{id:"211328",title:"Prof.",name:"Jane",middleName:null,surname:"Reeves",slug:"jane-reeves",fullName:"Jane Reeves"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8063",title:"Food Security in Africa",subtitle:null,isOpenForSubmission:!1,hash:"8cbf3d662b104d19db2efc9d59249efc",slug:"food-security-in-africa",bookSignature:"Barakat Mahmoud",coverURL:"https://cdn.intechopen.com/books/images_new/8063.jpg",editedByType:"Edited by",editors:[{id:"92016",title:"Dr.",name:"Barakat",middleName:null,surname:"Mahmoud",slug:"barakat-mahmoud",fullName:"Barakat Mahmoud"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10118",title:"Plant Stress Physiology",subtitle:null,isOpenForSubmission:!1,hash:"c68b09d2d2634fc719ae3b9a64a27839",slug:"plant-stress-physiology",bookSignature:"Akbar Hossain",coverURL:"https://cdn.intechopen.com/books/images_new/10118.jpg",editedByType:"Edited by",editors:[{id:"280755",title:"Dr.",name:"Akbar",middleName:null,surname:"Hossain",slug:"akbar-hossain",fullName:"Akbar Hossain"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9157",title:"Neurodegenerative Diseases",subtitle:"Molecular Mechanisms and Current Therapeutic Approaches",isOpenForSubmission:!1,hash:"bc8be577966ef88735677d7e1e92ed28",slug:"neurodegenerative-diseases-molecular-mechanisms-and-current-therapeutic-approaches",bookSignature:"Nagehan Ersoy Tunalı",coverURL:"https://cdn.intechopen.com/books/images_new/9157.jpg",editedByType:"Edited by",editors:[{id:"82778",title:"Ph.D.",name:"Nagehan",middleName:null,surname:"Ersoy Tunalı",slug:"nagehan-ersoy-tunali",fullName:"Nagehan Ersoy Tunalı"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9961",title:"Data Mining",subtitle:"Methods, Applications and Systems",isOpenForSubmission:!1,hash:"ed79fb6364f2caf464079f94a0387146",slug:"data-mining-methods-applications-and-systems",bookSignature:"Derya Birant",coverURL:"https://cdn.intechopen.com/books/images_new/9961.jpg",editedByType:"Edited by",editors:[{id:"15609",title:"Dr.",name:"Derya",middleName:null,surname:"Birant",slug:"derya-birant",fullName:"Derya Birant"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8686",title:"Direct Torque Control Strategies of Electrical Machines",subtitle:null,isOpenForSubmission:!1,hash:"b6ad22b14db2b8450228545d3d4f6b1a",slug:"direct-torque-control-strategies-of-electrical-machines",bookSignature:"Fatma Ben Salem",coverURL:"https://cdn.intechopen.com/books/images_new/8686.jpg",editedByType:"Edited by",editors:[{id:"295623",title:"Associate Prof.",name:"Fatma",middleName:null,surname:"Ben Salem",slug:"fatma-ben-salem",fullName:"Fatma Ben Salem"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"644",title:"Geochronology",slug:"geochronology",parent:{title:"Geology and Geophysics",slug:"geology-and-geophysics"},numberOfBooks:1,numberOfAuthorsAndEditors:12,numberOfWosCitations:17,numberOfCrossrefCitations:4,numberOfDimensionsCitations:16,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"geochronology",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"3837",title:"Geochronology",subtitle:"Methods and Case Studies",isOpenForSubmission:!1,hash:"2b1836bafece610b56c6334e338be74c",slug:"geochronology-methods-and-case-studies",bookSignature:"Nils-Axel Morner",coverURL:"https://cdn.intechopen.com/books/images_new/3837.jpg",editedByType:"Edited by",editors:[{id:"15619",title:"Dr.",name:"Nils-Axel",middleName:null,surname:"Morner",slug:"nils-axel-morner",fullName:"Nils-Axel Morner"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:1,mostCitedChapters:[{id:"47225",doi:"10.5772/58835",title:"Layered PGE Paleoproterozoic (LIP) Intrusions in the N-E Part of the Fennoscandian Shield — Isotope Nd-Sr and 3He/4He Data, Summarizing U-Pb Ages (on Baddeleyite and Zircon), Sm-Nd Data (on Rock-Forming and Sulphide Minerals), Duration and Mineralizatio",slug:"layered-pge-paleoproterozoic-lip-intrusions-in-the-n-e-part-of-the-fennoscandian-shield-isotope-nd-s",totalDownloads:1737,totalCrossrefCites:2,totalDimensionsCites:8,book:{slug:"geochronology-methods-and-case-studies",title:"Geochronology",fullTitle:"Geochronology - Methods and Case Studies"},signatures:"T. Bayanova, F. Mitrofanov, P. Serov, L. Nerovich, N. Yekimova, E.\nNitkina and I. Kamensky",authors:[{id:"144199",title:"Prof.",name:"Tamara",middleName:null,surname:"Bayanova",slug:"tamara-bayanova",fullName:"Tamara Bayanova"}]},{id:"46984",doi:"10.5772/58630",title:"Varve Chronology",slug:"varve-chronology",totalDownloads:1681,totalCrossrefCites:0,totalDimensionsCites:3,book:{slug:"geochronology-methods-and-case-studies",title:"Geochronology",fullTitle:"Geochronology - Methods and Case Studies"},signatures:"Nils-Axel Mörner",authors:[{id:"15619",title:"Dr.",name:"Nils-Axel",middleName:null,surname:"Morner",slug:"nils-axel-morner",fullName:"Nils-Axel Morner"}]},{id:"47051",doi:"10.5772/58549",title:"Quaternary Geochronology Using Accelerator Mass Spectrometry (AMS) – Current Status of the AMS System at the TONO Geoscience Center",slug:"quaternary-geochronology-using-accelerator-mass-spectrometry-ams-current-status-of-the-ams-system-at",totalDownloads:1862,totalCrossrefCites:2,totalDimensionsCites:2,book:{slug:"geochronology-methods-and-case-studies",title:"Geochronology",fullTitle:"Geochronology - Methods and Case Studies"},signatures:"Akihiro Matsubara, Yoko Saito-Kokubu, Akimitsu Nishizawa,\nMasayasu Miyake, Tsuneari Ishimaru and Koji Umeda",authors:[{id:"52811",title:"Dr.",name:"Koji",middleName:null,surname:"Umeda",slug:"koji-umeda",fullName:"Koji Umeda"},{id:"170321",title:"Dr.",name:"Akihiro",middleName:null,surname:"Matsubara",slug:"akihiro-matsubara",fullName:"Akihiro Matsubara"}]}],mostDownloadedChaptersLast30Days:[{id:"47225",title:"Layered PGE Paleoproterozoic (LIP) Intrusions in the N-E Part of the Fennoscandian Shield — Isotope Nd-Sr and 3He/4He Data, Summarizing U-Pb Ages (on Baddeleyite and Zircon), Sm-Nd Data (on Rock-Forming and Sulphide Minerals), Duration and Mineralizatio",slug:"layered-pge-paleoproterozoic-lip-intrusions-in-the-n-e-part-of-the-fennoscandian-shield-isotope-nd-s",totalDownloads:1737,totalCrossrefCites:2,totalDimensionsCites:8,book:{slug:"geochronology-methods-and-case-studies",title:"Geochronology",fullTitle:"Geochronology - Methods and Case Studies"},signatures:"T. Bayanova, F. Mitrofanov, P. Serov, L. Nerovich, N. Yekimova, E.\nNitkina and I. Kamensky",authors:[{id:"144199",title:"Prof.",name:"Tamara",middleName:null,surname:"Bayanova",slug:"tamara-bayanova",fullName:"Tamara Bayanova"}]},{id:"47052",title:"Luminescence Chronology",slug:"luminescence-chronology",totalDownloads:2078,totalCrossrefCites:0,totalDimensionsCites:2,book:{slug:"geochronology-methods-and-case-studies",title:"Geochronology",fullTitle:"Geochronology - Methods and Case Studies"},signatures:"Ken Munyikwa",authors:[{id:"169465",title:"Dr.",name:"Ken",middleName:null,surname:"Munyikwa",slug:"ken-munyikwa",fullName:"Ken Munyikwa"}]},{id:"47051",title:"Quaternary Geochronology Using Accelerator Mass Spectrometry (AMS) – Current Status of the AMS System at the TONO Geoscience Center",slug:"quaternary-geochronology-using-accelerator-mass-spectrometry-ams-current-status-of-the-ams-system-at",totalDownloads:1862,totalCrossrefCites:2,totalDimensionsCites:2,book:{slug:"geochronology-methods-and-case-studies",title:"Geochronology",fullTitle:"Geochronology - Methods and Case Studies"},signatures:"Akihiro Matsubara, Yoko Saito-Kokubu, Akimitsu Nishizawa,\nMasayasu Miyake, Tsuneari Ishimaru and Koji Umeda",authors:[{id:"52811",title:"Dr.",name:"Koji",middleName:null,surname:"Umeda",slug:"koji-umeda",fullName:"Koji Umeda"},{id:"170321",title:"Dr.",name:"Akihiro",middleName:null,surname:"Matsubara",slug:"akihiro-matsubara",fullName:"Akihiro Matsubara"}]},{id:"47054",title:"In situ U-Pb Dating Combined with SEM Imaging on Zircon — An Analytical Bond for Effective Geological Recontructions",slug:"in-situ-u-pb-dating-combined-with-sem-imaging-on-zircon-an-analytical-bond-for-effective-geological-",totalDownloads:1865,totalCrossrefCites:0,totalDimensionsCites:1,book:{slug:"geochronology-methods-and-case-studies",title:"Geochronology",fullTitle:"Geochronology - Methods and Case Studies"},signatures:"Annamaria Fornelli, Giuseppe Piccarreta and Francesca Micheletti",authors:[{id:"169456",title:"Dr.",name:"Annamaria",middleName:null,surname:"Fornelli",slug:"annamaria-fornelli",fullName:"Annamaria Fornelli"},{id:"169457",title:"Dr.",name:"Francesca",middleName:null,surname:"Micheletti",slug:"francesca-micheletti",fullName:"Francesca Micheletti"},{id:"169458",title:"Dr.",name:"Giuseppe",middleName:null,surname:"Piccarreta",slug:"giuseppe-piccarreta",fullName:"Giuseppe Piccarreta"}]},{id:"46984",title:"Varve Chronology",slug:"varve-chronology",totalDownloads:1681,totalCrossrefCites:0,totalDimensionsCites:3,book:{slug:"geochronology-methods-and-case-studies",title:"Geochronology",fullTitle:"Geochronology - Methods and Case Studies"},signatures:"Nils-Axel Mörner",authors:[{id:"15619",title:"Dr.",name:"Nils-Axel",middleName:null,surname:"Morner",slug:"nils-axel-morner",fullName:"Nils-Axel Morner"}]},{id:"46954",title:"Geochronology From The Castelo Branco Pluton (Portugal) — Isotopic Methodologies",slug:"geochronology-from-the-castelo-branco-pluton-portugal-isotopic-methodologies",totalDownloads:1453,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"geochronology-methods-and-case-studies",title:"Geochronology",fullTitle:"Geochronology - Methods and Case Studies"},signatures:"Antunes Imhr",authors:[{id:"169469",title:"Dr.",name:"Isabel",middleName:null,surname:"Antunes",slug:"isabel-antunes",fullName:"Isabel Antunes"},{id:"170573",title:"Prof.",name:"Ana",middleName:null,surname:"Neiva",slug:"ana-neiva",fullName:"Ana Neiva"},{id:"170574",title:"Prof.",name:"Maria",middleName:null,surname:"Silva",slug:"maria-silva",fullName:"Maria Silva"}]}],onlineFirstChaptersFilter:{topicSlug:"geochronology",limit:3,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[{type:"book",id:"10176",title:"Microgrids and Local Energy Systems",subtitle:null,isOpenForSubmission:!0,hash:"c32b4a5351a88f263074b0d0ca813a9c",slug:null,bookSignature:"Prof. Nick Jenkins",coverURL:"https://cdn.intechopen.com/books/images_new/10176.jpg",editedByType:null,editors:[{id:"55219",title:"Prof.",name:"Nick",middleName:null,surname:"Jenkins",slug:"nick-jenkins",fullName:"Nick Jenkins"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:8,limit:8,total:1},route:{name:"profile.detail",path:"/profiles/171948/hevertton-barbosa",hash:"",query:{},params:{id:"171948",slug:"hevertton-barbosa"},fullPath:"/profiles/171948/hevertton-barbosa",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()