Absolute Protein Binding Free Energy Simulations for Ligands with Multiple Poses, a Thermodynamic Path That Avoids Exhaustive Enumeration of the Poses.

ABSTRACT: We propose a free energy calculation method for receptor-ligand binding, which have multiple binding poses that avoids exhaustive enumeration of the poses. For systems with multiple binding poses, the standard procedure is to enumerate orientations of the binding poses, restrain the ligand to each orientation, and then, calculate the binding free energies for each binding pose. In this study, we modify a part of the thermodynamic cycle in order to sample a broader conformational space of the ligand in the binding site. This modification leads to more accurate free energy calculation without performing separate free energy simulations for each binding pose. We applied our modification to simple model host-guest systems as a test, which have only two binding poses, by using a single decoupli

SUBMITTER: Sakae Y 

PROVIDER: S-EPMC7140983 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature