Title

Accelerating QM/MM Free Energy Computations via Intramolecular Force Matching

Document Type

Article

Publication Date

2018

Digital Object Identifier (DOI)

https://doi.org/10.1021/acs.jctc.8b00517

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.

Was this content written or created while at USF?

Yes

Citation / Publisher Attribution

Journal of Chemical Theory and Computation, v. 14, issue 12, p. 6327-6335

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