The sensitivity of conformational free energies of the alanine dipeptide to atomic site charges.

Abstract

Different atomic point charge sets are obtained for the alpha R and C7,eq conformations of the alanine dipeptide by fitting the charges of each conformation to the respective ab initio electrostatic potential surfaces both individually and simultaneously, in both the united atom and the all-atom representations. Using these charge sets, the sensitivity of the relative conformational aqueous free energies to the atomic site charges is investigated. For this particular system, we find that the solute-water contributions to the conformational free energy differences have a rather weak dependence on site charges; the calculated intramolecular contributions, however, show a rather strong dependence on the atomic site charges. It is suggested that the calculated results for the alanine dipeptide using a single, simultaneously fit set of charges for both conformations are in better agreement with experiments than the calculations carried out with charges determined individually for each conformation.