Enhanced-Sampling Simulations for the Estimation of Ligand Binding Kinetics: Current Status and Perspective.

ABSTRACT: The dissociation rate (k _off) associated with ligand unbinding events from proteins is a parameter of fundamental importance in drug design. Here we review recent major advancements in molecular simulation methodologies for the prediction of k _off. Next, we discuss the impact of the potential energy function models on the accuracy of calculated k _off values. Finally, we provide a perspective from high-performance computing and machine learning which might help improve such predictions.

SUBMITTER: Ahmad K 

PROVIDER: S-EPMC9216551 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature