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Accelerated Computation of Free Energy Profile at ab Initio Quantum Mechanical/Molecular Mechanics Accuracy via a Semi-Empirical Reference Potential. II. Recalibrating Semi-Empirical Parameters with Force Matching

preprint
submitted on 15.07.2019 and posted on 16.07.2019 by Xiaoliang Pan, Pengfei Li, Junming Ho, Jingzhi Pu, Ye Mei, Yihan Shao
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 AI-QM/MM corrected reaction free energy profile. For three model reactions (identity SN2 reaction, Menshutkin reaction, and glycine proton transfer reaction) in aqueous solution and one enzyme reaction (Claisen arrangement in chorismate mutase), our simulations using recalibrated PM3 SE-QM Hamiltonians well reproduced AI-QM/MM free energy profiles (at the B3LYP/6-31G* level of theory) all within 1 kcal/mol with a 20 to 45 fold reduction in the computer time.

History

Email Address of Submitting Author

yihan.shao@ou.edu

Institution

University of Oklahoma

Country

USA

ORCID For Submitting Author

0000-0001-9337-341X

Declaration of Conflict of Interest

None.

Exports