Development of a Robust Indirect Approach for MM → QM Free Energy Calculations That Combines Force-Matched Reference Potential and Bennett's Acceptance Ratio Methods.

ABSTRACT: We use the PBE0/6-31G* density functional method to perform ab initio quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) simulations under periodic boundary conditions with rigorous electrostatics using the ambient potential composite Ewald method in order to test the convergence of MM → QM/MM free energy corrections for the prediction of 17 small-molecule solvation free energies and eight ligand binding free energies to T4 lysozyme. The "indirect" thermodynamic cycle for calculating free energies is used to explore whether a series of reference potentials improve the statistical quality of the predictions. Specifically, we construct a series of reference potentials that optimize a molecular mechanical (MM) force field's parameters to reproduce the ab initio QM/MM forc

SUBMITTER: Giese TJ 

PROVIDER: S-EPMC6834343 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature