A fixed-charge model for alcohol polarization in the condensed phase, and its role in small molecule hydration.
We present a simple optimization strategy for incorporating experimental dielectric response information on neat liquids in classical molecular models of alcohol. Using this strategy, we determine simple and transferable hydroxyl modulation rules that, when applied to an existing molecular parameter set, result in a newly dielectric corrected (DC) parameter set. We applied these rules to the general Amber force field (GAFF) to form an initial set of GAFF-DC parameters, and we found this to lead to significant improvement in the calculated dielectric constant and hydration free energy values for a wide variety of small molecule alcohol models. Tests of the GAFF-DC parameters in the SAMPL4 blind prediction event for hydration show these changes improve agreement with experiment. Surprisingly, these simple modifications also outperform detailed quantum mechanical electric field calculations using a self-consistent reaction field environment coupling term. This work provides a potential benchmark for future developments in methods for representing condensed-phase environments in electronic structure calculations.
Department of Chemistry, Oklahoma State University , Stillwater, Oklahoma 74078, United States.
Christopher J
CJ
Fennell
Karisa L
KL
Wymer
David L
DL
Mobley
D003198:Computer Simulation; D000431:Ethanol / Q000737:chemistry*; D006878:Hydroxides / Q000737:chemistry; D008956:Models, Chemical; D011789:Quantum Theory; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
D006878:Hydroxides; D014867:Water; D000431:Ethanol; C031356:hydroxide ion