Computer Simulation of Proton Transfers of Small Acids in Water

The potential experienced by an excess proton from the acetate ion solvated in water has been investigated, and a parameter set is presented which is suitable for molecular dynamics (MD) or mixed MD/quantum dynamics (QD) simulations and compatible with the GROMOS96 force field. A general procedure for deriving parameters for the proton potential is presented. The simulations started from five random configurations, energy minimized and equilibrated in both the deprotonated and the protonated state. In the case of weak acids such as the considered molecules, the proton transfer rate of both deprotonation and protonation of the solvated acid has been found to be considerably lower than the corresponding proton transfer rates between neighboring water molecules. The reaction free energy profile of a proton transfer reaction has been determined using umbrella sampling and thermodynamic integration. The results encourage the application of the mixed MD/QD simulation scheme to simulations of proton transfers from and to large biomolecules in water.