DYNAMICAL FLUCTUATING CHARGE FORCE-FIELDS - THE AQUEOUS SOLVATION OF AMIDES

The fluctuating charge (FQ) force field, a polarizable potential model in which point charges on atomic sites fluctuate in response to the e nvironment, is applied to the aqueous solvation of acetamide and trans - and cis-N-methylacetamide (NMA). Two parameters are assigned to each kind of atom, corresponding to an electronegativity and a hardness. T he FQ model accurately reproduces both the gas-phase and aqueous-phase charge distributions of these molecules and is therefore effective in treating the influence of functional group substitutions, conformatio n changes, and solvent on the charge distribution. The FQ model does t his in a way that is computationally efficient by propagating the char ges in time using an extended Lagrangian method. Solvation free energy calculations are done using both an explicit (FQ) solvent and a diele ctric continuum solvent. Both solvent models predict a negligible free energy difference between trans- and cis-NMA, in agreement with exper imental estimates. The explicit solvent calculations find that the fre e energy difference between NMA and acetamide is 0.5 +/- 0.8 kcal/mol, in good agreement, but of opposite sign, with the measured value of - 0.3 +/- 0.4 kcal/mol. The FQ/dielectric continuum calculations find th at this free energy difference is sensitive to the details of the solu te cavity, varying from 0.4 to 1.5 kcal/mol.