Quantum-classical molecular dynamics simulations of proton transfer processes in molecular complexes and in enzymes

A quantum-classical molecular dynamics model (QCMD) designed for simulations of proton or electron transfer processes in molecular systems is described and applied to several model problems. The primary goal of this work is the elucidation of enzymatic reactions. For example, using the QCMD model, the dynamics of key protons in an enzyme's active site might be described by the time-dependent Schroedinger equation while the dynamics of the remaining atoms are described using MD. The coupling between the quantum proton(s) and the classical atoms is accomplished via extended Hellmann-Feynman forces, as well as the time dependence of the potential energy function in the Schroedinger equation. The potential energy function is either parametrized prior to the simulations or can be computed using a parametrized valence bond (VB) method (QCMD/VB model). The QCMD method was used to simulate proton transfer in a proton bound ammonia-ammonia dimer as well as to simulate dissociation of a Xe-HI complex in its electronic excited state. The simulation results are compared with data obtained using a quantum-classical time-dependent self-consistent field method (Q/C TDSCF) and with results of fully quantum-dynamical simulations. Finally QCMD/VB simulations of a hydrolytic process catalyzed by phospholipase Az, including quantum-dynamical dissociation of a water molecule in the active site, are reported. To the best of our knowledge, these are the first simulations that explicitly use the time-dependent Schroedinger equation to describe enzyme catalytic activity.