Accelerating QM/MM Free Energy Computations via Intramolecular Force Matching
Digital Object Identifier (DOI)
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?
Citation / Publisher Attribution
Journal of Chemical Theory and Computation, v. 14, issue 12, p. 6327-6335
Scholar Commons Citation
Hudson, Phillip S.; Boresch, Stefan; Rogers, David M.; and Woodcock, H. Lee III, "Accelerating QM/MM Free Energy Computations via Intramolecular Force Matching" (2018). Chemistry Faculty Publications. 50.