Description

There are numerous excellent reviews on fragment-based drug discovery (FBDD), but there are to date no hand-holding guides or protocols with which one can embark on this orthogonal approach to complement traditional high throughput screening methodologies. This Methods in Enzymology volume offers the tools, practical approaches, and hit-to-lead examples on how to conduct FBDD screens. The chapters in this volume cover methods that have proven to be successful in generating leads from fragments, including chapters on how to apply computational techniques, nuclear magnetic resonance, surface plasma resonance, thermal shift and binding assays, protein crystallography, and medicinal chemistry in FBDD. Also elaborated by experienced researchers in FBDD are sample preparations of fragments, proteins, and GPCR as well as examples of how to generate leads from hits.

Key Features

Offers the tools, practical approaches, and hit-to-lead examples on how to conduct FBDD screens
The chapters in this volume cover methods that have proven to be successful in generating leads from fragments, including chapters on how to apply computational techniques, nuclear magnetic resonance, surface plasma resonance, thermal shift and binding assays, protein crystallography, and medicinal chemistry in FBDD

Readership

Researchers and students in cell, molecular and developmental biology

Table of Contents

Part I. Tools

1. Designing a Diverse High Quality Library for Crystallography Based FBDD Screening

Brett A. Tounge, Michael H. Parker

2. Preparation of Protein Samples for NMR Structure, Function, and Small-Molecule Screening Studies

Thomas B. Acton, Rong Xiao, James Aramini, William A. Buchwald, Colleen Ciccosanti, Ken Conover, Keith Hamilton, Yuanpeng Janet Huang, Haleema Janjua, Paolo Rossi, Seema Sharma, G.V.T.Swapna, Huang Wang, Li Zhao, Gaetano T. Montelione

3. Key Factors for Successful Generation of Protein-Fragment Structures: Requirements on Protein, Crystals, and Technology

Anja Jestel, Stefan Steinbacher

4. Automated Crystal Amplification and Compound Dispensation for FBDD Analysis

Francis A. Lewandowski, Brett A. Tounge, Cynthia M. Milligan

5. Hardware and Protocols for Rapid Fragment Based Structure Determination

Richard S. Alexander, John C. Spurlino

6. Using Computational Techniques in Fragment-Based Drug Discovery

Renee L. DesJarlais

7. Computational Approaches to De Novo Discovery of Fragment Binding for Unprecedented Protein States

Zenon D. Konteatis, Jinming Zou, Anthony E. Klon, Siavash Meshkat

Part II. Practical Approaches

8. How to Avoid Rediscovering the Known

Lawrence C. Kuo

9. From Experimental Design to Data Analysis: A Comprehensive Walk-Through of Fragment Identification Using Surface Plasmon Resonance

Anthony M. Giannetti

10. Practical Aspects of NMR Based Fragment Screening

Christopher Lepre

11. Fluorescent Protein Thermal Shifts to Identify Low Molecular Weight Fragments

James K. Kranz, Matthew J. Todd

12. A

Details

No. of pages:
645
Language:
English
Copyright:
© 2011
Published:
Imprint:
Academic Press
eBook ISBN:
9780123812759
Print ISBN:
9780123812742

About the serial-volume-editor

Lawrence Kuo

Affiliations and Expertise

Merck Sharp & Dohme Research Laboratories, Merck & Co., West Point, Pennsylvania, U.S.A.