Computational Drug Discovery and Design

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 pK_a 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.