Part I: Drug Binding Site Prediction, Design, and Descriptors
1. A Molecular Dynamics Ensemble-based Approach for the Mapping of Druggable Binding Sites
Anthony Ivetac and J, Andrew McCammon
2. Analysis of Protein Binding Sites by Computational Solvent Mapping
David R. Hall, Dima Kozakov, and Sandor Vajda
3. Evolutionary Trace for Prediction and Redesign of Protein Functional Sites
Angela Wilkins, Serkan Erdin, Rhonald Lua, and Olivier Lichtarge
4. Information Entropic Function for Molecular Descriptor Profiling
Anne Mai Wasswrmann, Britta Nisius, Martin Vogt, and
Jürgen Bajorath
Part II: Virtual Screening of Large Compound Libraries: Including Molecular Flexibility
5. Expanding the Conformational Selection Paradigm in Protein-Ligand Docking
Guray Kuzu, Ozlem Keskin, Attila Gursoy, and Ruth Nussinov
6. Flexibility Analysis of Biomacromolecules with Application to Computer-aided Drug Design
Simone Fulle and Holger Gohlke
7.On the Use of Molecular Dynamics Receptor Conformations for Virtual Screening
Sara Nichols, Riccardo Baron, and J. Andrew McCammon
8. Virtual Ligand Screening Against Comparative Protein Structure Models
Hao Fan, John J. Irwin, and Andrej Sali
9.AMMOS Software: Method and Application
Tania Pencheva, David Lagorce, Ilza Pajeva, Bruno O. Villoutreix, and Maria A. Miteva
10.Rosetta Ligand Docking with Flexible XML Protocols
Gordon Lemmon and Jens Meiler
11.Normal Mode-Based Approaches in Receptor Ensemble Docking
Claudio N. Cavasotto
12. Application of Conformational Clustering in Protein-Ligand Docking
Giovanni Bottegoni, Walter Rocchia, and Andrea Cavalli
13. How to Benchmark Methods for Structure-based Virtual Screenin of Large Compound Libraries
Andrew J. Christofferson and Niu Huang
Part III: Prediction of Protein-Protein Docking and Interactions
14. AGGRESCAN: Method, Application, and Perspectives for Drug Design
Natalia S. de Groot, Virginia Castillo, Ricardo Graña, and Salvador Ventura Zamora
15. ATTRACT and PTOOLS: Open Source Programs for Protein-protein Docking
Sebastian Schneider, Adrien Saladin, Chantal Prevost, and Martin Zacharias
16. Prediction of Interacting Protein Residues using Sequence and Structure Data
Vedran Franke, Mile Sikic, and Kristian Vlahovicek
Part IV: Rescoring Docking Predictions
17. MM-GB/SA Rescoring of Docking Poses
Cristiano R.W. Guimarães
18. A Case Study of Scoring and Rescoring in Peptide Docking
Zunnan Huang and Chung Wong
19. The Solvated Interaction Energy (SIE) Method for Scoring Binding Affinities
Traian Sulea and Enrico Purisima
20. Linear Interaction Energy (LIE): Method and Applications in Drug Design
Hugo Guitiérrez-de-Terán and Johan Åqvist
Part V: Crucial Neglected Effects: Entropy, Solvent, and Protonation
21. Estimation of Conformational Entropy in Protein-Ligand Interactions: A Computational Prespective
Anton Polyansky, Ruben Zubac, and Bojan Zagrovic
22. Explicit Treatment of Water Molecules in Data-driven Protein-protein Docking: The Solvated HADDOCKing Approach
Panagotis L. Kastritis, Aalt D.J. van Dijk, and Alexandre M.J.J. Bonvin
23. Protein-water Interactions in MD Simulations: POPS/POPSCOMP Solvent Accessibility Analysis, Solvation Forces and Hydration Sites
Arianna Fornili, Flavia Autore, Nesrine Chakroun, Pierre Martinez, and Franca Fraternali
24. Computing the Thermodynamic Contributions of Interfacial Water
Zheng Li and Themis Lazaridis
25. Assignment of Protonation States in Proteins and Ligands: Combining pKa Prediction with Hydrogen Bonding Network Optimization
Elmar Krieger, Rob Hooft, Roland Dunbr
Due to the rapid and steady growth of available low-cost computer power, the use of computers for discovering and designing new drugs is becoming a central topic in modern molecular biology and medicinal chemistry. In Computational Drug Discovery and Design: Methods and Protocols expert researchers in the field provide key techniques to investigate biomedical applications for drug developments based on computational chemistry. These include methods and techniques from binding sites prediction to the accurate inclusion of solvent and entropic effects, from high-throughput screening of large compound databases to the expanding area of protein-protein inhibition, toward quantitative free-energy approaches in ensemble-based drug design using distributed computing. Written in the highly successful Methods in Molecular Biology™ series format, chapters include introductions to their respective topics, reference to software and open source analysis tools, step-by-step, readily reproducible computational protocols, and key tips on troubleshooting and avoiding known pitfalls.
Thorough and intuitive, Computational Drug Discovery and Design: Methods and Protocols aids scientists in the continuing study of state-of-the-art concepts and computer-based methodologies.
