A Constant-pH Hybrid Monte Carlo Method with a Configuration-Selection Scheme Using the Zero Energy Difference Condition: Elucidation of Molecular Diffusivity Correlated with a pH-Dependent Solvation Shell.

We have proposed a new constant-pH (CpH) hybrid Monte Carlo (MC) method with a configuration-selection (CS) scheme, called the CS-CpH method, to obtain pH-dependent physical properties within a framework of atomistic molecular simulation. The CS-CpH method consists of carrying out a short equilibrium molecular dynamics (MD) and a searching MD coupled with thermostats and barostats to generate physically plausible configurations with changed protonation states (PSs) that are subsequently accepted or rejected according to the Metropolis MC procedure. As an example, we have applied it to glutamic acid in aqueous solution and have demonstrated that it can work to generate reasonably the pH-dependent microscopic configuration ensemble compatible with the experimental pKa value and also to show interestingly the molecular diffusivity correlated with pH-dependent solvation shell. In conclusion, we believe that the present CS-CpH method becomes a quite useful tool to study the microscopic origin of various pH-dependent phenomena, interpreting them in the atomistic chemical processes.