Assessing models of force-dependent unbinding rates via infrequent metadynamics.

ABSTRACT: Protein-ligand interactions are crucial for a wide range of physiological processes. Many cellular functions result in these non-covalent "bonds" being mechanically strained, and this can be integral to proper cellular function. Broadly, two classes of force dependence have been observed-slip bonds, where the unbinding rate increases, and catch bonds, where the unbinding rate decreases. Despite much theoretical work, we cannot predict for which protein-ligand pairs, pulling coordinates, and forces a particular rate dependence will appear. Here, we assess the ability of MD simulations combined with enhanced sampling techniques to probe the force dependence of unbinding rates. We show that the infrequent metadynamics technique correctly produces both catch and slip bonding kinetics for model

SUBMITTER: Pena Ccoa WJ 

PROVIDER: S-EPMC8957391 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature