Molecular dynamics simulation of proton transport with quantum mechanically derived proton hopping rates (Q-HOP MD)

A very efficient scheme is presented to simulate proton transport by classi cal molecular dynamics simulation coupled with quantum mechanically derived proton hopping. Simulated proton transfer rates and proton diffusion const ants for an excess proton in a box of water molecules are in good agreement with experimental data and with previous simulations that employed empiric al valence bond (EVB) theory. For the first time, the proton occupancy of a n aspartic acid residue in water was computed directly by MD simulations. L ocally enhanced sampling or multi copy techniques were used to facilitate p roton release in simulations of an imidazole ring in a solvent box. Summari zing, a quasiclassical description of proton transfer dynamics has been abl e to capture important kinetic and thermodynamic features of these systems at less than 50% computational overhead compared to standard molecular dyna mics simulations. The method can be easily generalized to simulate the prot onation equilibria of a large number of titratable sites. This should make it an attractive method to study proton transport in large biological syste ms. (C) 2001 American Institute of Physics.