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/quantun 1 dynamics (QD) si mulations and compatible with the GROMOS96 force field. A general procedure for deriving parameters for the proton potential is presented. The simulat ions started from five random configurations, energy minimized and equilibr ated in both the deprotonated and the proronated state. In the case of weak acids such as the considered molecules, the proton transfer rate of both d sprotonation and protonation of the solvated acid has been found to be cons iderably lower than the corresponding proton transfer rates between neighbo ring water molecules. The reaction free energy profile of a proton transfer reaction has been determined using umbrella sampling and thermodynamic int egration. The results encourage the application of the mixed MD/QD simulati on scheme to simulations of proton transfers from and to large biomolecules in water.