Enhancing water sampling of buried binding sites using nonequilibrium candidate Monte Carlo.

ABSTRACT: Water molecules can be found interacting with the surface and within cavities in proteins. However, water exchange between bulk and buried hydration sites can be slow compared to simulation timescales, thus leading to the inefficient sampling of the locations of water. This can pose problems for free energy calculations for computer-aided drug design. Here, we apply a hybrid method that combines nonequilibrium candidate Monte Carlo (NCMC) simulations and molecular dynamics (MD) to enhance sampling of water in specific areas of a system, such as the binding site of a protein. Our approach uses NCMC to gradually remove interactions between a selected water molecule and its environment, then translates the water to a new region, before turning the interactions back on. This approach of gradua

SUBMITTER: Bergazin TD 

PROVIDER: S-EPMC7904576 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature