Enhancing Sampling of Water Rehydration on Ligand Binding: A Comparison of Techniques.

ABSTRACT: Water often plays a key role in protein structure, molecular recognition, and mediating protein-ligand interactions. Thus, free energy calculations must adequately sample water motions, which often proves challenging in typical MD simulation time scales. Thus, the accuracy of methods relying on MD simulations ends up limited by slow water sampling. Particularly, as a ligand is removed or modified, bulk water may not have time to fill or rearrange in the binding site. In this work, we focus on several molecular dynamics (MD) simulation-based methods attempting to help rehydrate buried water sites: BLUES, using nonequilibrium candidate Monte Carlo (NCMC); grand, using grand canonical Monte Carlo (GCMC); and normal MD. We assess the accuracy and efficiency of these methods in rehydrati

SUBMITTER: Ge Y 

PROVIDER: S-EPMC9241631 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature