Fragment Based Drug Design

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