Physics ABC Seminar: "MixMD: Mapping Protein Surfaces to Discover Druggable Allosteric Sites", Prof. Heather A. Carlson, University of Michigan

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Date: September 29, 2020
Time: 3:30 p.m. - 4:30 p.m.
Location: Zoom
Category: Seminar

MixMD: Mapping Protein Surfaces to Discover Druggable Allosteric Sites

Heather A. Carlson
Chair of Medicinal Chemistry and Director of the Interdepartmental Program in Medicinal Chemistry
College of Pharmacy, University of Michigan

Cosolvent molecular dynamics (MD) simulations use small organic probe molecules to sample along a protein surface and identify binding "hotspots". The benefits of this approach are the protein can adapt to the presence of the cosolvents and the cosolvents must compete with water to interact with the protein. Accommodating protein flexibility and hydration effects are two leading challenges in structure-based drug discovery. Advances in cosolvent MD will be presented including applications to allosteric systems, prediction of bridging water molecules, identification of cryptic binding sites, and assessment of target druggability. Though these approaches are resource intensive, they have the promise of identifying previously unknown regulatory sites on proteins, which could significantly increase the number of drug targets available to treat a wide variety of medical disorders.


· P Ghanakota, HA Carlson. Driving structure-based drug discovery through cosolvent molecular dynamics. J. Med. Chem. 2016, 59, 10383-10339.
· P Ghanakota, HA Carlson. Moving beyond active-site detection: MixMD applied to allosteric systems. J. Phys. Chem. B 2016, 120, 8685-8695.
· SE Graham, HA Carlson. Predicting displaceable water sites using mixed-solvent molecular dynamics. J. Chem. Info. Model. 2018, 58, 305-314.
· RD Smith, HA Carlson. Identification of cryptic binding sites using MixMD with standard and accelerated molecular dynamics. J. Chem. Info. Model. 2020, in review.



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