Optimizing the Calculation of Free Energy Differences in Nonequilibrium Work SQM/MM Switching Simulations.

ABSTRACT: A key step during indirect alchemical free energy simulations using quantum mechanical/molecular mechanical (QM/MM) hybrid potential energy functions is the calculation of the free energy difference ΔA^low→high between the low level (e.g., pure MM) and the high level of theory (QM/MM). A reliable approach uses nonequilibrium work (NEW) switching simulations in combination with Jarzynski's equation; however, it is computationally expensive. In this study, we investigate whether it is more efficient to use more shorter switches or fewer but longer switches. We compare results obtained with various protocols to reference free energy differences calculated with Crooks' equation. The central finding is that fewer longer switches give better converged results. As few as 200 suff

SUBMITTER: Scholler A 

PROVIDER: S-EPMC9036525 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature