Reversibly Sampling Conformations and Binding Modes Using Molecular Darting.

ABSTRACT: Sampling multiple binding modes of a ligand in a single molecular dynamics simulation is difficult. A given ligand may have many internal degrees of freedom, along with many different ways it might orient itself in a binding site or across several binding sites, all of which might be separated by large energy barriers. We have developed a novel Monte Carlo move called molecular darting (MolDarting) to reversibly sample between predefined binding modes of a ligand. Here, we couple this with nonequilibrium candidate Monte Carlo (NCMC) to improve acceptance of moves. We apply this technique to a simple dipeptide system, a ligand binding to T4 lysozyme L99A, and ligand binding to HIV integrase to test this new method. We observe significant increases in acceptance compared to uniformly samplin

SUBMITTER: Gill SC 

PROVIDER: S-EPMC8121195 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature