Potential of mean force of water-proton bath and molecular dynamic simulation of proteins at constant pH.

An advanced implicit solvent model of water-proton bath for protein simulations at constant pH is presented. The implicit water-proton bath model approximates the potential of mean force of a protein in water solvent in a presence of hydrogen ions. Accurate and fast computational implementation of the implicit water-proton bath model is developed using the continuum electrostatic Poisson equation model for calculation of ionization equilibrium and the corrected MSR6 generalized Born model for calculation of the electrostatic atom-atom interactions and forces. Molecular dynamics (MD) method for protein simulation in the potential of mean force of water-proton bath is developed and tested on three proteins. The model allows to run MD simulations of proteins at constant pH, to calculate pH-dependent properties and free energies of protein conformations. The obtained results indicate that the developed implicit model of water-proton bath provides an efficient way to study thermodynamics of biomolecular systems as a function of pH, pH-dependent ionization-conformation coupling, and proton transfer events.