Accelerating QM/MM Free Energy Computations Via Intramolecular Force Matching

Overview

Journal J Chem Theory Comput

Publisher American Chemical Society

Specialties Biochemistry
Chemistry

Date 2018 Oct 10

PMID 30300543

Citations 25

Authors

Phillip S Hudson

Stefan Boresch

David M Rogers

H Lee Woodcock

Affiliations

Soon will be listed here.

Abstract

The calculation of free energy differences between levels of theory has numerous potential pitfalls. Chief among them is the lack of overlap, i.e., ensembles generated at one level of theory (e.g., "low") not being good approximations of ensembles at the other (e.g., "high"). Numerous strategies have been devised to mitigate this issue. However, the most straightforward approach is to ensure that the "low" level ensemble more closely resembles that of the "high". Ideally, this is done without increasing computational cost. Herein, we demonstrate that by reparametrizing classical intramolecular potentials to reproduce high level forces (i.e., force matching) configurational overlap between a "low" (i.e., classical) and "high" (i.e., quantum) level can be significantly improved. This procedure is validated on two test cases and results in vastly improved convergence of free energy simulations.

Citing Articles

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