| Abstract
| - The electrostatic energy component of classical force fields oftenincludes some of the polarization energycomponent implicitly through the choice of atomic charges. In thisand the subsequent articles we describeprogress toward separating and accurately calculating bothelectrostatic and polarization energies. In thepresent contribution the distributed point charge representation ofelectrostatics is retained. Charges derivedfrom several quantum chemical models including electron correlation atvarious levels are compared. Wefound that ignoring electron correlation in deriving charges for ourforce field can result in an error of severalkcal mol-1 in free energy differencesimulations, and that this error can be comparable to the effect ofignoringpolarization. We conclude that the accurate treatment ofpolarization in force fields also requires an accuratetreatment of electron correlation. The work is based on therelatively new MPFIT charge fitting procedure(Ferenczy, G. G. J. Comput. Chem.1991,12, 913; Chipot, C.; et. al.J. Phys. Chem.1993,97,6628), whichproduces point charges comparable to conventional molecularelectrostatic potential-derived charges. Thesenew charges are slightly less polar and more transferable and containmore chemical sense, but they are stillconformationally dependent. The significance of different levelsof electron correlation in these charges wasexamined through regression analysis, to determine scalingrelationships between the charges, and throughfree energy difference simulations, to determine the effect of usingalternative charge sets. The free energycalculations indicate that the Becke−Lee, Yang, and Parr nonlocaldensity functional method gives chargessimilar to second-order Møller−Plessett perturbation theory.The charges are shown to be insensitive to theprecision of the quadrature used in the density functionalcalculations. For polar molecules, these methodsgenerally gave free energies of hydration which were significantlysmaller than those computed using Hartree−Fock charges. When the Hartree−Fock charges are scaled toreproduce the higher quality charges, the erroris usually reduced, but is still significant in some cases. Sincemany force fields effectively exploit thepolarity of the Hartree−Fock charges to mimic the effects ofpolarization in an ad hoc way, this result hasimportant implications for force field design, as mentioned above.It is suggested that the electron densitycalculated by the density functional method is a suitable startingpoint to derive distributed multipole sets foruse in force fields which include explicit polarization.
|
