Fragment-Based Methods in Drug Discovery

2015
ISBN: 978-1-4939-2485-1
Verlag: Springer

Buch, Englisch, Band 1289, 230 Seiten, Format (B × H): 183 mm x 260 mm, Gewicht: 6542 g

Reihe: Methods in Molecular Biology

This volume covers the techniques necessary for a successful fragment-based drug design project, beginning from defining the problem in terms of preparing the protein model, identifying potential binding sites, and the consideration of various candidate fragments for simulation. The second part discusses the technical aspects that various methods have used to simulate fragment binding to a target protein by using Monte Carlo, molecular dynamics, and docking algorithms. After simulations, fragments are assembled into molecules using a variety of approaches, which are explored next. A discussion of design strategies and consideration of drug-like properties is included as part of the design process at this stage. Finally, several examples of successful fragment-based drug design projects are presented. Written for the Methods in Molecular Biology series, this work contains the kind of detailed description and implementation advice to encourage success in the lab.

Practical and cutting-edge, Fragment-Based Methods in Drug Discovery takes into account the great accomplishments in the field to provide an ideal guide for researchers continuing to investigate this exciting area of pharmacological study.

Zielgruppe

Professional/practitioner

Autoren/Hrsg.

Klon, Anthony E.

Fachgebiete

• Medizin | Veterinärmedizin Medizin | Public Health | Pharmazie | Zahnmedizin Medizinische Fachgebiete Pharmakologie, Toxikologie
• Medizin | Veterinärmedizin Medizin | Public Health | Pharmazie | Zahnmedizin Pharmazie
• Naturwissenschaften Biowissenschaften Proteinforschung

Inhaltsverzeichnis

Part I: Preparation

1. Solvation Methods for Protein-Ligand Docking

            Rachelle J. Bienstock

2. Binding Site Druggability Assessment in Fragment-Based Drug Design

            Yu Zhou and Niu Huang

3. Generating "Fragment-Based Virtual Library" Using Pocket Similarity Search of Ligand-Receptor Complexes

            Raed S. Khashan

4. Virtual Fragment Preparation for Computational Fragment-Based Drug Design

            Jennifer L. Ludington

5. Fragment Library Design: Using Cheminformatics and Expert Chemists to Fill Gaps in Existing Fragment Libraries

            Peter S. Kutchukian, Sung-Sau So, Christian Fischer, and Chris L. Waller

Part II: Simulation

6. Protocol for Fragment Hopping

            Kevin B. Teuscher and Haitao Ji

7. Site Identification by Ligand Competitive Saturation (SILCS) Simulations for Fragment-Based Drug Design

            Christina E. Faller, E. Prabhu Raman, Alexander D. MacKerell, Jr., and Olgun Guvench

8. A Computational Fragment-Based De Novo Design Protocol Guided by Ligand Efficiency Indices (LEI)

            Álvaro Cortés-Cabrera, Federico Gago, and Antonio Morreale

9. Scoring Functions for Fragment-Based Drug Discovery

            Jui-Chih Wang and Jung-Hsin Lin

Part III: Design

10. Computational Methods for Fragment-Based Ligand Design: Growing and Linking

            Rachelle J. Bienstock

11. Design Strategies for Computational Fragment-Based Drug Design

            Zenon D. Konteatis

12. Protein Binding Site Analysis for Drug Discovery Using a Computational Fragment-Based Method

            Jennifer L. Ludington

Part IV: Case Studies

13. Fragment-Based Design of Kinase Inhibitors: A Practical Guide

            Jon A. Erickson

14. Designing a Small Molecule Erythropoietin Mimetic

            Frank Guarnieri

15. Designing an Orally Available Non-Toxic p38 Inhibitor with a Fragment-Based Strategy

            Frank Guarnieri