Structure-Based Drug Discovery

ISBN-13: 9781617795190 / Angielski / Twarda / 2012 / 385 str.

Leslie W. Tari

Opis

The last decade has seen the confluence of several enabling technologies that have allowed protein crystallographic methods to live up to their true potential. Taken together, the numerous recent advances have made it possible to tackle difficult biological targets with a high probability of success: intact bacterial ribosomes have been structurally elucidated, as well as eukaryotic trans-membrane proteins like the potassium channel and GPCRs. It is now possible for medicinal chemists to have access to structural information on their latest small molecule candidates bound to the therapeutic target within days of compound synthesis, allowing structure guided ligand optimization to occur in "real time." Structure-Based Drug Discovery presents an array of methods used to generate crystal structures of biological macromolecules, how to leverage the structural information to design novel ligands anew, and how to iteratively optimize hits and convert them to leads. Written in the successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls.Authoritative and easily accessible, Structure-Based Drug Discovery aims to provide scientists interested in adding SBDD to their arsenal of drug discovery methods with well-honed, up-to-date methodologies.

Recenzje

From the reviews:

"By collecting effective state-of-the-arts methodologies, technologies, and protocols, the book provide a consistent guide pertaining to the complex, multi- and interdisciplinary SBDD operation. This book is recommended for researchers getting involved in SBDD projects as well as for scientists involved in the most diverse areas of protein chemistry, structural biology, medicinal chemistry, and chemical informatics." (Julianna Kardos, Structural Chemistry, Vol. 23, 2012)

Spis treści

1. The Utility of Structural Biology in Drug Discovery

                Leslie W. Tari

 

2. Genetic Construct Design and Recombinant Protein Expression for Structural Biology

                Suzanne C. Edavettal, Michael J. Hunter, and Ronald V. Swanson

 

3. Purification of Proteins for Crystallographic Applications

                Daniel C. Bensen

 

4. Protein Crystallization for Structure-Based Drug Design

                Isaac D. Hoffman

 

5. X-Ray Sources and High-Throughput Data Collection Methods

                Gyorgy Snell

 

6. The Use of Molecular Graphics in Structure-Based Drug Design

                Paul Emsley and Judit É. Debreczeni

 

7. Crystallographic Fragment Screening

                John Badger

 

8. The Role of Enzymology in a Structure-Based Drug Discovery Program: Bacterial DNA Gyrase

                Mark L. Cunningham

 

9. Leveraging Structural Information for the Discovery of New Drugs: Computational Methods

                Toan B. Nguyen, Sergio E. Wong, and Felice C. Lightstone

 

10. Chemical Informatics – Using Molecular Shape Descriptors in Structure-Based Drug Design

                Andy Jennings

 

11. Accounting for Solvent in Structure-Based Drug Design

                Leslie W. Tari

 

12. Structure-Based Drug Design on Membrane Protein Targets: Human Integral Membrane Protein 5-Lipoxygenase-Activating Protein

                Andrew D. Ferguson

 

13. Application of SBDD to the Discovery of New Antibacterial Drugs

                John Finn

 

14. Leveraging SBDD in Protein Therapeutic Development: Antibody Engineering

                Gary L. Gilliland, Jinquan Luo, Omid Vafa, and Juan Carlos Almagro

 

15. A Medicinal Chemistry Perspective on Structure-Based Drug Design and Development

                Shawn P. Maddaford