Interfacing ab initio Quantum Mechanical Method with Classical Drude Osillator Polarizable Model for Molecular Dynamics Simulation of Chemical Reactions.

In order to further improve the accuracy and applicability of combined quantum mechanical/molecular mechanical (QM/MM) methods, we have interfaced the ab initio QM method with the classical Drude oscillator polarizable MM force field (ai-QM/MM-Drude). Different coupling approaches have been employed and compared: 1. the conventional dual self-consistent-field (SCF) procedure; 2. the direct SCF scheme, in which QM densities and MM Drude positions are converged simultaneously; 3. the micro-iterative SCF scheme, in which the Drude positions of the polarizable model are fully converged during each self-consistent field (SCF) step of QM calculations; 4. the one-step-Drude-update scheme, in which the MM Drude positions are updated only once instead of fully converged during each molecular dynamics (MD) step. The last three coupling approaches are found to be efficient and can achieve the desired convergence in a similar number of QM SCF steps comparing with the corresponding QM method coupled to a non-polarizable force field. The feasibility and applicability of the implemented ai-QM/MM-Drude approach have been demonstrated by carrying out Born-Oppenheimer molecular dynamics simulations with the umbrella sampling method to determine potentials of mean force for both the methyl transfer reaction of the methyl chlorine-chlorine ion system and the glycine intra-molecular proton transfer reaction in aqueous solution. Our results indicate that the ai-QM/MM-Drude approach is very promising, which provides a better description of QM/MM interactions while can achieve quite similar computational efficiency in comparison with the corresponding conventional ab initio QM/MM method.