Acceleration of Ab Initio QM/MM Calculations under Periodic Boundary Conditions by Multiscale and Multiple Time Step Approaches.

Development of multiscale ab initio quantum mechanical and molecular mechanical (AI-QM/MM) method for periodic boundary molecular dynamics (MD) simulations and their acceleration by multiple time step approach are described. The developed method achieves accuracy and efficiency by integrating the AI-QM/MM level of theory and the previously developed semiempirical (SE) QM/MM-Ewald sum method [J. Chem. Theory Comput. 2005, 1, 2] extended to the smooth particle-mesh Ewald (PME) summation method. In the developed methods, the total energy of the simulated system is evaluated at the SE-QM/MM-PME level of theory to include long-range QM/MM electrostatic interactions, which is then corrected on the fly using the AI-QM/MM level of theory within the real space cutoff. The resulting energy expression enables decomposition of total forces applied to each atom into forces determined at the low-level SE-QM/MM method and correction forces at the AI-QM/MM level, to integrate the system using the reversible reference system propagator algorithm. The resulting method achieves a substantial speed-up of the entire calculation by minimizing the number of time-consuming energy and gradient evaluations at the AI-QM/MM level. Test calculations show that the developed multiple time step AI-QM/MM method yields MD trajectories and potential of mean force profiles comparable to single time step QM/MM results. The developed method, together with message passing interface (MPI) parallelization, accelerates the present AI-QM/MM MD simulations about 30-fold relative to the speed of single-core AI-QM/MM simulations for the molecular systems tested in the present work, making the method less than one order slower than the SE-QM/MM methods under periodic boundary conditions.