Reaction Path Force Matching: A New Strategy of Fitting Specific Reaction Parameters for Semiempirical Methods in Combined QM/MM Simulations

Abstract

We present a general strategy of reparametrizing semiempirical (SE) methods against ab initio (AI) methods for combined quantum mechanical and molecular mechanical (QM/MM) simulations of specific chemical reactions in condensed phases. The resulting approach, designated Reaction Path Force Matching (RP-FM), features cycles of sampling configurations along a reaction path on an efficient SE/MM potential energy surface (PES) and adjusting specific reaction parameters (SRPs) in the SE method such that the atomic forces computed at the target AI/MM level are reproduced. Iterative applications of the RP-FM cycle make possible achieving the accuracy of AI/MM simulations without explicitly sampling the computationally expensive AI/MM PES. The bypassed sampling, nevertheless, is implicitly accomplished through the aid of the efficient SE-SRP/MM PES, on which the target-level reaction path is expected to be obtained upon convergence. We demonstrate the effectiveness of the RP-FM procedure for a symmetric proton transfer reaction in the gas phase and in solution. The remarkable agreements between the RP-FM optimized SE-SRP methods and the target AI method on various properties, including energy profiles, potential of mean force free energy profiles, atomic forces, charge populations, and solvation effects, suggest that RP-FM can be used as an efficient and reliable strategy for simulating condensed-phase chemical reactions.