Danial Sabri Dashti, Yilin Meng and Adrian E. Roitberg . pH-Replica Exchange Molecular Dynamics in Proteins Using a Discrete Protonation Method
J. Phys. Chem. B, 2012, 116 (30), pp 8805–8811, 2012-06-13
Abstract: Protonation equilibria in biological molecules modulates structure, dynamics, and function. A pH-replica exchange molecular dynamics (pH-REMD) method is described here to improve the coupling between conformational and protonation sampling. Under a Hamiltonian replica exchange setup, conformations are swapped between two neighboring replicas, which themselves are at different pHs. The method has been validated on a series of biological systems. We applied pH-REMD to a series of model compounds, to an terminally charged ADFDA pentapeptide, and to a heptapeptide derived from the ovomucoid third domain (OMTKY3). In all of those systems, the predicted pKa by pH-REMD is very close to the experimental value and almost identical to the ones obtained by constant pH molecular dynamics (CpH MD). The method presented here, pH-REMD, has the advantage of faster convergence properties due to enhanced sampling of both conformation and protonation spaces.