Fluctuating Charge, Polarizable Dipole, and Combined Models: Parameterization from ab Initio Quantum Chemistry

We performed studies of fluctuating charge, fluctuating dipole, and combined models for substituted benzenes and concluded that dipoles are necessary to avoid errors in important cases. Force fields incorporating fluctuating dipoles for alanine, serine, and phenylalanine were developed that accurately reproduce both relative conformational energies and cooperative many-body energies as given by ab initio quantum chemical calculations. The polarization model was fit to quantum chemical calculations of changes in the electrostatic potential (ESP) induced by applied perturbations. The electrostatic model was completed by adding fixed charges fit to the zero-field quantum chemical ESP. All intramolecular and Lennard-Jones parameters, and some torsional parameters, were taken from the OPLS-AA force field of Jorgensen and co-workers. Key torsional parameters were refit to quantum chemical structures and energies.