Applications of Biophysical Methods in Small-Molecule Drug Discovery (Laptop Required)

Sunday, February 6, 2022

8:30 AM – 4:30 PM

Location: 103

Christian Bergsdorf, PhD

Labhead
Novartis Institutes for Biomedical Research, Basel-Stadt, Switzerland
Geoffrey Holdgate

Senior Principal Scientist, HTS
AstraZeneca R&D UK, Discovery Sciences, Hit Discovery, England, United Kingdom

Instructors will be presenting virtually. Laptop will be required to access the course.

Additional Fees Apply
-- visit the Short Course Program section for more information.

This short course will provide an introduction to mass spectrometry and the range of potential applications within drug discovery. We will cover the basic principles of mass spectrometry including the differences between the array of ionization modalities and detectors available today. While mass spectrometry has contributed significantly to drug discovery, recent advances are enabling high throughput screening applications.

Who Should Attend:

Lab scientists with an interest in understanding the fundamentals of mass spectrometry

Lab managers interested in understanding how mass spectrometry can impact drug discovery

Budget holders who are considering investing in mass spectrometry technology

Assay development scientists and HTS screeners who want to understand how mass spectrometry can impact their research

How You Will Benefit From This Course:

Get a better understanding of the principles of mass spectrometry

Gain an understanding of the diversity of instruments and ionization techniques

Understanding of where mass spectrometry can be applied with impact in drug discovery

Learn about recent developments in mass spectrometry

Course Topics:

Overview of the most relevant biochemical biophysics/ label-free technologies for screening and lead finding.

Main technologies discussed in more detail: Mass Spectrometry; NMR; Calorimetry (DSC, ITC); SPR; Interferometry; Resonance Waveguide Grating (aka Corning Epic); thermal protein denaturation and aggregation assays (DSF aka Thermofluor, DSLS aka Stargazer, CETSA; nanoDSF); Dynamic Light Scattering; Microscale Thermophoresis (NanoTemper).

Understand which technology and combinations thereof fits best to answer specific questions throughout the entire drug discovery process.

Grasp how biophysics can support assay development for screening and how biophysical data can be used to fuel medicinal chemistry design.

Course Pre-Reading Requirements:

General introduction into affinity-based methods and their application in Drug Discovery:
(articles which describe how the approaches work, caveats, and a summary of their impact)

Integrating biophysics with HTS-driven drug discovery projects
Folmer, Rutger H.A.
Drug Discovery Today, March 2016, Vol.21(3), pp.491-498
Identifier: ISSN: 1359-6446 ; DOI: 10.1016/j.drudis.2016.01.011

Applications of Biophysics in High-Throughput Screening Hit Validation
Genick, Christine Clougherty ; Barlier, Danielle ; Monna, Dominique ; Brunner, Reto ; Bé, Céline ; Scheufler, Clemens ; Ottl, Johannes
Journal of biomolecular screening, June 2014, Vol.19(5), pp.707-14
Identifier: E-ISSN: 1552-454X ; PMID: 24695619 Version:1 ; DOI: 10.1177/1087057114529462

Biophysics in Drug Discovery: impact, challenges, and opportunities,
Jean-Paul Renaud, Chun wa Chung, U. Helena Danielson, Ursula Egner, Michael Hennig, Roderick E. Hubbard, and Herbert Nar
Nature Reviews, August 2016, Vol.15(10), pp. 679-98 DOI: 10.1038/nrd.2016.123

Background Information on each technology/approach:

DLS:
Making sense of Brownian motion: colloid characterization by dynamic light scattering
Hassan, Puthusserickal A ; Rana, Suman ; Verma, Gunjan
Langmuir: the ACS journal of surfaces and colloids, 13 January 2015, Vol.31(1), pp.3-12
Identifier: E-ISSN: 1520-5827 ; PMID: 25050712 Version:1 DOI: 10.1021/la501789z

TSA:
Thermal denaturation assays in chemical biology
Senisterra, Guillermo ; Chau, Irene ; Vedadi, Masoud
Assay and drug development technologies, April 2012, Vol.10(2), pp.128-36
Identifier: E-ISSN: 1557-8127 ; PMID: 22066913 Version:1 DOI: 10.1089/adt.2011.0390

CETSA:
The cellular thermal shift assay for evaluating drug target interactions in cells
Jafari, Rozbeh ; Almqvist, Helena ; Axelsson, Hanna ; Ignatushchenko, Marina ; Lundbäck, Thomas ; Nordlund, Pär ; Martinez Molina, Daniel
Nature protocols, September 2014, Vol.9(9), pp.2100-22
Identifier: E-ISSN: 1750-2799 ; PMID: 25101824 Version:1 DOI: 10.1038/nprot.2014.138

MST:
Microscale Thermophoresis: Interaction analysis and beyond
Jerabek-Willemsen, Moran ; André, Timon ; Wanner, Randy ; Roth, Heide Marie ; Duhr, Stefan ; Baaske, Philipp ; Breitsprecher, Dennis
Journal of Molecular Structure, 5 December 2014, Vol.1077, pp.101-113
Identifier: ISSN: 0022-2860 ; DOI: 10.1016/j.molstruc.2014.03.009

MS:
Affinity selection-mass spectrometry screening techniques for small molecule drug discovery
Annis, D. Allen ; Nickbarg, Elliot ; Yang, Xianshu ; Ziebell, Michael R. ; Whitehurst, Charles E.
Current Opinion in Chemical Biology, 2007, Vol.11(5), pp.518-526

NMR:
Parallel screening of low molecular weight fragment libraries: do differences in methodology affect hit identification?
Wielens, Jerome ; Headey, Stephen J ; Rhodes, David I ; Mulder, Roger J ; Dolezal, Olan ; Deadman, John J ; Newman, Janet ; Chalmers, David K ; Parker, Michael W ; Peat, Thomas S ; Scanlon, Martin J
Journal of biomolecular screening, February 2013, Vol.18(2), pp.147-59
Identifier: E-ISSN: 1552-454X ; PMID: 23139382 Version:1 DOI: 10.1177/1087057112465979

SPR:
Biomolecular interaction analysis in drug discovery using surface plasmon resonance technology
Huber, W ; Mueller, F
Current Pharmaceutical Design, 2006, Vol.12(31), pp.3999-4021
Identifier: ISSN: 1381-6128

RWG:
Resonant waveguide grating for monitoring biomolecular interactions
Wu, Meng ; Li, Min
Methods in molecular biology (Clifton, N.J.), 2015, Vol.1278, pp.139-52
Identifier: E-ISSN: 1940-6029 ; PMID: 25859947 Version:1 ; DOI: 10.1007/978-1-4939-2425-7_8

ITC:
Direct measurement of protein binding energetics by isothermal titration calorimetry
Leavitt, Stephanie ; Freire, Ernesto
Current Opinion in Structural Biology, 2001, Vol.11(5), pp.560-566
Identifier: ISSN: 0959-440X ; DOI: 10.1016/S0959-440X(00)00248-7

Xray:
Effective and Emerging Strategies for utilizing Structure in Drug Discovery
Brown, Ka ; Davenport, R ; Ward, Se
Drugs Of The Future, 2015 Apr, Vol.40(4), pp.251-256 [Peer Reviewed Journal]
Identifier: ISSN: 0377-8282 ; DOI: 10.1358/dof.2015.040.04.2314768