Efficient Sampling of Cavity Hydration in Proteins with Nonequilibrium Grand Canonical Monte Carlo and Polarizable Force Fields.

ABSTRACT: Prediction of the hydration levels of protein cavities and active sites is important to both mechanistic analysis and ligand design. Due to the unique microscopic environment of these buried water molecules, a polarizable model is expected to be crucial for an accurate treatment of protein internal hydration in simulations. Here we adapt a nonequilibrium candidate Monte Carlo approach for conducting grand canonical Monte Carlo simulations with the Drude polarizable force field. The GPU implementation enables the efficient sampling of internal cavity hydration levels in biomolecular systems. We also develop an enhanced sampling approach referred to as B-walking, which satisfies detailed balance and readily combines with grand canonical integration to efficiently calculate quantitativ

SUBMITTER: Deng J 

PROVIDER: S-EPMC11663258 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature