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, identification of cryptic binding sites, and applications to undruggable systems. Though these approaches are resource intensive, they only require short MD simulations and they have the promise of identifying previously unknown regulatory sites on proteins. This could significantly increase the number of drug targets available to treat a wide variety of medical disorders.

MixMD: Mapping protein surfaces to discover druggable allosteric sites

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.