Applied Biophysics for Drug Discovery

Donald Huddler, Edward R. Zartler, Donald Huddler, Edward R. Zartler

• Publisher: Wiley
• Year: 2017
• Print ISBN: 9781119099482
• eBook ISBN: 9781119099505
• Edition: 1
• Topic: Biological Sciences
• Subtopic: Biophysics
• Index: Biological Sciences

Applied Biophysics for Drug Discovery is a guide to new techniques and approaches to identifying and characterizing small molecules in early drug discovery. Biophysical methods are reasserting their utility in drug discovery and through a combination of the rise of fragment-based drug discovery and an increased focus on more nuanced characterisation of small molecule binding, these methods are playing an increasing role in discovery campaigns. 

This text emphasizes practical considerations for selecting and deploying core biophysical method, including but not limited to ITC, SPR, and both ligand-detected and protein-detected NMR.

Topics covered include:

•          Design considerations in biophysical-based lead screening

•          Thermodynamic characterization of protein-compound interactions

•          Characterizing targets and screening reagents with HDX-MS

•          Microscale thermophoresis methods (MST)

•          Screening with Weak Affinity Chromatography

•          Methods to assess compound residence time

•          1D-NMR methods for hit identification

•          Protein-based NMR methods for SAR development

•          Industry case studies integrating multiple biophysical methods

This text is ideal for academic investigators and industry scientists planning hit characterization campaigns or designing and optimizing screening strategies.

Table of contents

• Cover
• Title Page
• Table of Contents
• List of Contributors
• 1 Introduction
• 2 Thermodynamics in Drug Discovery
• 3 Tailoring Hit Identification and Qualification Methods for Targeting Protein–Protein Interactions
• 4 Hydrogen–Deuterium Exchange Mass Spectrometry in Drug Discovery ‐ Theory, Practice and Future
• 5 Microscale Thermophoresis in Drug Discovery
• 6 SPR Screening: Applying the New Generation of SPR Hardware
• 7 Weak Affinity Chromatography (WAC)
• 8 1D NMR Methods for Hit Identification
• 9 Protein‐Based NMR Methods Applied to Drug Discovery
• 10 Applications of Ligand and Protein‐Observed NMR in Ligand Discovery
• 11 Using Biophysical Methods to Optimize Compound Residence Time
• 12 Applying Biophysical and Biochemical Methods to the Discovery of Allosteric Modulators of the AAA ATPase p97
• 13 Driving Drug Discovery with Biophysical Information: Application to Staphylococcus aureus Dihydrofolate Reductase (DHFR)
• 14 Assembly of Fragment Screening Libraries: Property and Diversity Analysis
• Index
• End User License Agreement