Fragment Based Drug Design book cover

Fragment Based Drug Design

Tools, Practical Approaches, and Examples

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.


Researchers and students in cell, molecular and developmental biology

Included in series
Methods in Enzymology

Hardbound, 645 Pages

Published: March 2011

Imprint: Academic Press

ISBN: 978-0-12-381274-2


  • 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 HTS Reporter Displacement Assay for Fragment Screening and Fragment Evolution Towards Leads with Optimized Binding Affinity, Binding Kinetics, and Kinetic Selectivity

    Lars Neumann

    13. Fragment Screening of Stabilized G-Protein Coupled Receptors Using Biophysical Methods

    Miles Congreve, Fiona H. Marshall, David Myszka, Gregg Siegal

    14. Predicting the Success of a Fragment Screening by X-Ray Crystallography

    Douglas Davies, Lance Stewart

    15. Fragment Screening Purely with Protein Crystallography

    John C. Spurlino

    16. Structure Density Relationship Based FBDD

    Marta C. Abad, Xuqing Zhang, Alan C. Gibbs

    Part III. Lead Generation Examples

    17. Lead Generation and Examples - Opinions Regarding How to Follow Up Hits

    Masaya Orita, Kazuki Ohno, Masaichi Warizaya, Yasushi Amano, Tatsuya Niimi

    18. High Throughput Thermodynamics for Selection of Fragment Hits and Guidance of Fragment Evolution

    Lars Neumann

    19. Medicinal Chemistry Inspired Fragment Based Drug Discovery

    James C. Lanter, Xuqing Zhang, Zhihua Sui

    20. Experiences in Fragment-Based Lead Discovery

    Roderick E. Hubbard, James B. Murray

    21. Advancing Fragment Binders to Lead Like Compounds Using Ligand and Protein Based NMR Spectroscopy

    Till Maurer

    22. Effective Progression of NMR-Directed Fragment Hits

    Hugh Eaton, Daniel Wyss

    23. Fragment Screening of Infectious Disease Targets in a Structural Genomics Environment

    Douglas Davies, Lance Stewart


advert image