pH-replica exchange molecular dynamics in proteins using a discrete protonation method.
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 pK(a) 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.
Department of Physics and Quantum Theory Project, University of Florida, Gainesville, Florida 32611-8435, USA.
Danial
D
Sabri Dashti
Yilin
Y
Meng
Adrian E
AE
Roitberg
D000465:Algorithms; D000595:Amino Acid Sequence; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism; D011522:Protons
D009842:Oligopeptides; D011522:Protons