Accelerated computation of free energy profile at ab initio quantum mechanical/molecular mechanical accuracy via a semi-empirical reference potential. II. Recalibrating semi-empirical parameters with force matching.

ABSTRACT: An efficient and accurate reference potential simulation protocol is proposed for producing ab initio quantum mechanical/molecular mechanical (AI-QM/MM) quality free energy profiles for chemical reactions in a solvent or macromolecular environment. This protocol involves three stages: (a) using force matching to recalibrate a semi-empirical quantum mechanical (SE-QM) Hamiltonian for the specific reaction under study; (b) employing the recalibrated SE-QM Hamiltonian (in combination with molecular mechanical force fields) as the reference potential to drive umbrella samplings along the reaction pathway; and (c) computing AI-QM/MM energy values for collected configurations from the sampling and performing weighted thermodynamic perturbation to acquire an AI-QM/MM corrected reaction free energ

SUBMITTER: Pan X 

PROVIDER: S-EPMC6761017 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature