Software and Techniques for Bio-Molecular Modelling Azat Mukhametov Published by Austin Publications LLC Published Date: December 01, 2016 Online Edition available at http://austinpublishinggroup.com/ebooks For reprints, please contact us at [email protected] All book chapters are Open Access distributed under the Creative Commons Attribution 4.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of the publication. Upon publication of the eBook, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work, identifying the original source. Statements and opinions expressed in the book are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published chapters. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Software and Techniques for Bio-Molecular Modelling | www.austinpublishinggroup.com/ebooks 1 Copyright Mukhametov A.This book chapter is open access distributed under the Creative Commons Attribution 4.0 International License, which allows users to download, copy and build upon published articles even for com- mercial purposes, as long as the author and publisher are properly credited. We consider to publish more books on the topics of drug design, molecular modelling, and structure-activity relationships. Those, wishing to contribute a chapter or article please contact this Book’s Editor by e-mail: [email protected] Software and Techniques for Bio-Molecular Modelling | www.austinpublishinggroup.com/ebooks 2 Copyright Mukhametov A.This book chapter is open access distributed under the Creative Commons Attribution 4.0 International License, which allows users to download, copy and build upon published articles even for com- mercial purposes, as long as the author and publisher are properly credited. Table of Contents Preface 5 Software 1.GROMPALA: a membrane-implicit modelling method to screen lipid- 8 interacting molecules. Steinhauer S, Crowet JM, Brasseur R and Lins L 2. AtlasCBS: a graphic tool to map the content of structure-activity databases. 19 Abad-Zapatero C 3. Modeller: an application for homology modeling. Singh R and Gaur P 38 Techniques 4. Protein structure prediction using molecular homology modelling. Barbosa 48 LCB and Carrijo RS 5. Structure, shape and electrostatic based virtual screening to discover small 58 molecule therapeutics. Parkesh R, Bhutani I and Madathil R 6. Introduction to the molecular dynamics of biomolecules. Morton-Blake DA 75 7. GPU accelerated molecular dynamics simulations for predition of protien- 90 Chong WL, Gautam V, Zain SM, Noorsaadah AR and Lee VS peptide and protein-protein binding affinity. 8. Knowledge formalization and high-throughput data visualization using 107 signaling network maps. Kondratova M, Barillot E, Zinovyev A and Kuperstein I Case Studies 9. Neuro-ligands optimization using molecular modeling. Chaturvedi S and 131 Mishra Anil K 10. Rational drug discovery: virtual screening of Den-2 non-competitive 147 inhibitors. Heh CH, Othman R, Yusof R and Rahman NA Software and Techniques for Bio-Molecular Modelling | www.austinpublishinggroup.com/ebooks 3 11. Comparative evaluation of docking programs: a case study with small 156 peptidic ligands. Kumar M, Tiwari P and Kaur P 12. Protein interaction study of novel mutants of human Hsp70 and Ad5 motif 171 (PNLVP). Elengoe A and Hamdan S 183 antagonist. Divakar S, Hariharan S and Ramanathan M 13. Structure based drug design in identification of novel androgen receptor 14. Hepatitis C viral polymerase inhibition using directly acting antivirals: a 197 computational approach. Elfiky AA, Gawad WA and Elshemey WM. 209 Muchtaridi 15. Application of structure and ligand-based drug design for finding lead compounds16. Molecular from dynamics natural product of E. source:coli Undecaprenyl case of influenza Diphosphate targeted. Synthase: 222 asymmetry in a homodimer. Newhouse EI, Alam M and Mukhametov A 17. Molecular dynamics simulations and molecular docking approaches in 237 Torabizadeh H SponsorsEndoinulinase and Advertisements chemical modification. Venture Pharmaceuticals Ltd 247 Software and Techniques for Bio-Molecular Modelling | www.austinpublishinggroup.com/ebooks 4 Preface The purpose of this book is to introduce new researchers into the field of Bio-Molecular Modelling. The field lays at intersection of such disciplines as Biology, Chemistry, Physics, and Computer Sciences. It is not surprising that researchers with respective backgrounds are attracted. Historically, modelling techniques applied to discovery and development of new bio-active compounds, were ligand-based. These are methods of quantitative structure-activity (QSAR) and structure-property (QSPR) studies. To date, these methods include multiple techniques. Linear regression analysis, support vector machines, random forest, naive Bayes, and artificial neural networks are just some examples that utilize massive mathematical apparatus. With introduction of protein structure determination methods and exponential increase in computer power, structure-based methods of designing bio-active compounds became also available. Modelling techniques got fast developing being applied to the challenges of life sciences (pharmaceutical, bio-technology, and agricultural sciences). These are search for biologically active molecules with targeted properties, development of special purpose proteins for industry, and fundamental studies of biological processes at molecular level. Bio-Molecular Modelling includes various sub-fields. Bio-informatics lays at intersection of biology and computer sciences. Chemo-informatics utilizes computer sciences to operate with chemical structures. Theoretical bio-physics applies methods of computational physics to biology challenges. This way the fields of Bio-Molecular Modelling develop extensively and intensively in various directions. Nova days Bio-Molecular Modelling includes multiple techniques. Methods of homology modelling let model three-dimensional structures of proteins based on the sequence of target protein and x-ray structural data of the template protein(s). Automated computational docking approaches make it possible to study the way small molecules may interact with bio-molecular targets. Being utilized to large library of ligands, it gets name of virtual screening. Pharmacophore modelling techniques let make pharmacophore models based on the structures of ligands Softwareor protein-ligand and Techniques complexes for Bio-Molecular for following Modelling pharmacophore-based | www.austinpublishinggroup.com/ebooks virtual screening of small5 Copyright Mukhametov A.This book chapter is open access distributed under the Creative Commons Attribution 4.0 International License, which allows users to download, copy and build upon published articles even for com- mercial purposes, as long as the author and publisher are properly credited. molecular ligands. Techniques of Molecular Dynamics simulations let computationally model dynamics of bio-molecules in native environment. Atomic-level interactions between parts of bio-molecules or their fragments can be studied with Quantum Chemistry approaches. Bio- Informatics approaches let understand interactions between bio-molecular targets and select key ones for Bio-Molecular Modelling. The listed are not all topics and fields of Bio-Molecular Modelling. However, these are the approaches which formed ground for future developments. Multiple methods and approaches are arising currently. Structurally, this Book “Software and Techniques for Bio-Molecular Modelling” consists of three parts: “Software”, “Techniques”, and “Case Studies”. Modern and powerful software is a key component for Bio-Molecular Modelling. These are complex packages, small applications, as desktop as network based. Databases can also be considered with software. “Software” – includes small chapters on software packages, and algorithms, available as on open-source as on commercial basis. Each article gives information on software, algorithms involved, purposes, pros and cons, license terms, references. Chapters on special-purpose applications are included. These are GROMPALA (a membrane- implicit modelling method to screen lipid-interacting molecules) by Dr. Laurence Lins; AtlasCBS (a graphic tool to map the content of structure-activity databases) by Dr. Cele Abad-Zapatero; and Modeller (an application for homology modelling) by Dr. Raghvendra Singh. Many techniques for Bio-Molecular Modelling, are included into the “Techniques” part of the Book. Each chapter includes introduction, background, technique description, references. All of the techniques described have been successfully applied to bio-molecular challenges by scientists in the field. These are the technique for Homology Modelling: Protein structure prediction using molecular homology modelling, by Dr. Luiz Carlos Bertucci Barbosa. Technique for Virtual Screening: Structure, shape and electrostatic based virtual screening to discover small molecule therapeutics, by Dr. Raman Parkesh. Techniques for Molecular Dynamics Simulations: