A replica exchange umbrella sampling (REUS) approach to predict host-guest binding free energies in SAMPL8 challenge.

ABSTRACT: In this study, we report binding free energy calculations of various drugs-of-abuse to Cucurbit-[8]-uril as part of the SAMPL8 blind challenge. Force-field parameters were obtained from force-matching with different quantum mechanical levels of theory. The Replica Exchange Umbrella Sampling (REUS) approach was used with a cylindrical restraint to enhance the sampling of host-guest binding. Binding free energy was calculated by pulling the guest molecule from one side of the symmetric and cylindrical host, then into and through the host, and out the other side (bidirectional) as compared to pulling only to the bound pose inside the cylindrical host (unidirectional). The initial results with force-matched MP2 parameter set led to RMSE of 4.68 [Formula: see text] from experimental values. How

SUBMITTER: Ghorbani M 

PROVIDER: S-EPMC8131287 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature