Applied Biophysics for Drug Discovery

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.

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

List of Contributors1. IntroductionDonald Huddler2. Thermodynamics in Drug DiscoveryOBrienMarkova&Holdgate3. Tailoring Hit Identification and Qualification Methods for Targeting Protein-Protein InteractionsBjörn Walse, Andrew P. Turnbull, Susan M. Boyd4. HYDROGEN DEUTERIUM EXCHANGE MASS SPECTROMETRY IN DRUG DISCOVERYThorleif Lavold, Roman Zubarev and Juan Astorga-Wells5. MICROSCALE THERMOPHORESIS IN DRUG DISCOVERYTanja Bartoschik, Melanie Maschberger, Alessandra Feoli, Timon André, Philipp Baaske, Stefan Duhr and Dennis Breitsprecher6. SPR Screening - Applying the new generation of SPR hardwareKartik Narayan and Steve Carroll7. Weak Affinity Chromatography (WAC)Sten Ohlson* and Minh-Dao Duong-Thi8. 1D NMR Methods for Hit IdentificationMary J Harner, Guille Metzler, Caroline A Fanslau, Luciano Mueller, William J Metzler9. Protein-Based NMR Methods Applied to Drug DiscoveryAlessio Bortoluzzi, Alessio Ciulli10. Applications of Ligand and Protein-observed NMR in DiscoveryIsabelle KrimmConclusion11. Using Biophysical Methods to Optimize Compound Residence TimeG. A. Holdgate, P. Rawlins, M. Bista, C. J. Stubbs12. Applying biophysical and biochemical methods to the discovery of allosteric modulators of the AAA ATPase p97Stacie L. Bulfer and Michelle R. Arkin13. Driving Drug Discovery with Biophysical Information - Application to Staphylococcus aureus Dihydrofolate Reductase (DHFR)Parag Sahasrabudhe, Veerabahu Shanmugasundaram, Mark Flanagan, Kris A. Borzilleri, Holly Heaslet, Anil Rane, Alex McColl, Tim Subashi, George Karam, Ron Sarver, Melissa Harris, Boris A. Chrunyk, Chakrapani Subramanyam, Thomas V. Magee, Kelly Fahnoe, Brian Lacey, Henry Putz, J. Richard Miller, Jaehyun Cho, Arthur Palmer III and Jane M. Withka14. Assembly of fragment screening libraries: Property and diversity analysisBradley C. Doak, Craig J. Morton, Jamie S. Simpson & Martin J. ScanlonIndex