The NADase SARM1 (sterile alpha and TIR motif containing 1) is a key executioner of axon degeneration and there is great interest in developing SARM1 enzyme inhibitors as candidate therapies for multiple neurodegenerative diseases.
Through a combined approach of X-ray crystallography and cryo-EM we uncovered the molecular mechanism of SARM1 inhibition by a compound (DSRM-3716), demonstrating that it undergoes a base-exchange reaction with the nicotinamide moiety of NAD+, and that the transferase product is the bona fide inhibitor. Further more we reveal the activated state of SARM1 for the first time.
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Neuroscience,
Medicinal Chemistry,
Articles & Whitepapers,
Structural Biology & Protein Science
Watch the webinar to learn more about exciting new developments in predictive toxicology!
About the Webinar
In this webinar, John Barker, SVP Global Head of Protein Sciences discusses bacterial infections and global health within anti-infectives. John gave this talk at the Oxford Global Discovery UK event in October 2021.
About the Speaker
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John Barker, PhD FRSB
Senior Vice President, Global Head of Protein Sciences | Evotec
Currently responsible for more than 150 scientists across four sites, Princeton NJ, Abingdon UK, Toulouse and Hamburg. Team delivering Protein Production, Structural Biology and Cellular Sciences both internally and to Evotec’s partnerships. Over the past 18 years built from the ground up the current Evotec structural biology unit, now with more than 30 PhD scientists, one of the largest units in industry. Supporter of UK industry as the Industrial Life Science representative on the Diamond Scientific Advisory Board. John has worked on more than 40 collaborations across a range of drug discovery projects including multiple structure and fragment guided programmes in all therapeutic areas.
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Videos & Webinars,
Structural Biology & Protein Science,
Anti-Infectives
In this article, we discuss the role of structure-based virtual screening in drug discovery.
The publication covers:
- an overview of structural-based virtual screening and the importance of selecting the most appropriate protocol for affinity estimation calculations
- the development of an automated calibration process implemented in a Knime workflow consisting of 4 steps:
- preparation of a protein test set with structures and models of the target
- preparation of a compound test set with target-related ligands and decoys
- automatic test of 24 scoring/rescoring protocols for each target structure and model
- graphical display of the results
- demonstration of the application of this tool in setting up an optimal protocol for structure-based virtual screening against Retinoid X Receptor alpha
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Tags:
Articles & Whitepapers,
Structural Biology & Protein Science
