Preface...
Table of Contents...
Contributing Authors...
1. Current and Future Challenges in GPCR Drug Discovery
Sid Topiol
2. Characterization of Ligand Binding to GPCRs through Computational Methods
Silvana Vasile, Mauricio Esguerra, Willem Jespers, Ana Oliveira, Jessica Sallander, Johan Åqvist, and Hugo Gutiérrez-de-Terán
3. Breakthrough in GPCR Crystallography and its Impact on Computer-Aided Drug Design
Antonella Ciancetta and Kenneth A. Jacobson
4. A Structural Framework for GPCR Chemogenomics: What's in a Residue Number?
Márton Vass, Albert J. Kooistra, Stefan Verhoeven, David Gloriam, Iwan J.P. de Esch, and Chris de Graaf
5. GPCR Homology Model Generation for Lead Optimization
Christofer S. Tautermann
6. GPCRs: What Can We Learn from Molecular Dynamics Simulations?
Naushad Velgy, George Hedger, and Philip C. Biggin
7. Methods of Exploring Protein-Ligand Interactions to Guide Medicinal Chemistry Efforts
r>Paul Labute
8. Exploring GPCR-Ligand Interactions with the Fragment Molecular Orbital (FMO) Method
Ewa I. Chudyk, Laurie Sarrat, Matteo Aldeghi, Dmitri G. Fedorov, Mike J. Bodkin, Tim James, Michelle Southey, Roger Robinson, Inaki Morao, and Alexander Heifetz
9. Molecular Basis of Ligand Dissociation from G Protein-Coupled Receptors and Predicting Residence Time
Dong Guo and Adriaan P. IJzerman
10. Methodologies for the Examination of Water in GPCRs
Andrea Bortolato, Benjamin G. Tehan, Robert T. Smith, and Jonathan S. Mason
11. Methods for Virtual Screening of GPCR Targets: Approaches and Challenges
Jason B. Cross
12. Approaches for Differentiation and Interconverting GPCR Agonists and Antagonists
Przemysław Miszta, Jakub Jakowiecki, Ewelina Rutkowska, Maria Turant, Dorota Latek, and Sławomir Filipek
13. Opportunities and Challenges in the Discovery of Allosteric Modulators of GPCRs
Damian Bartuzi, Agnieszka A. Kaczor, and Dariusz Matosiuk
14. Challenges and Opportunities in Drug Discovery of Biased Ligands
Ismael Rodríguez-Espigares, Agnieszka A. Kaczor, Tomasz Maciej Stepniewski, and Jana Selent
15. Synergistic Use of GPCR Modeling and SDM Experiments to Understand Ligand Binding
Andrew Potterton, Alexander Heifetz, and Andrea Townsend-Nicholson
16. Computational Support of Medicinal Chemistry Effort in Industrial Setting
Daniel F. Ortwine
17. Investigating Small-Molecule Ligand Binding to G Protein-Coupled Receptors with Biased or Unbiased Molecular Dynamics Simulations
Kristen A. Marino and Marta Filizola
18. Ligand-Based Methods in GPCR Computer-Aided Drug Design
Paul C. D. Hawkins and Gunther Stahl
19. Computational Methods Used in Hit-to-Lead and Lead Optimization Stages of Structure-Based Drug Discovery
Alexander Heifetz, Michelle Southey, Inaki Morao, Andrea Townsend-Nicholson, and Mike J. Bodkin
20. Cheminformatics in the Service of GPCR Drug Discovery
Tim James
21. Modeling and Deorphanization of Orphan GPCRs
Constantino Diaz, Patricia Angelloz-Nicoud, and Emilie Pihan
This volume looks at modern computational strategies and techniques used in GPCR drug discovery including structure and ligand-based approaches and cheminformatics. The chapters in this book describe how these approaches can be applied to address key drug discovery issues, such as receptor structure modelling, function and dynamics, prediction of protein-water-ligand interactions and binding kinetics, free energy of binding, interconversion between agonists and antagonists, deorphanization of GPCRs, and the discovery of biased and allosteric modulators. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary software and tools, step-by-step, readily reproducible modelling protocols, and tips on troubleshooting and avoiding known pitfalls.
Cutting-edge and unique,Computational Methods for GPCR Drug Discovery is a valuable resource for structural and molecular biologists, computational and medicinal chemists, pharmacologists, and drug designers.
