TOWARD IMPROVED FORCE-FIELDS .2. EFFECTIVE DISTRIBUTED MULTIPOLES

This is the second of a series of papers discussing the possibility of separating and accurately calculating electrostatic and polarization energies in simulations using classical force fields. A method is desc ribed for determining a set of effective distributed multipoles which have significantly improved convergence properties in evaluating the e lectrostatic interaction energy between molecules. These fitted multip oles are derived to reproduce the electrostatic potential and its deri vatives as calculated from a full distributed multipole analysis. The method is based on previous work on the determination of multipole-fit ted charges (Ferenczy, G. G. J. Comput. Chem. 1991, 12, 913; Chipot et al. J. Phys. Chem. 1993, 97, 6628) and does not involve the use of a numerical grid. In applications on model systems, fitted charges and d ipoles are able to reproduce both the interaction energy and the optim ized geometry obtained from a full distributed multipole analysis. Pot ential-derived charges, however, result in significant errors when the molecules are in close proximity to each other. The method was also u sed to investigate a possible reason why norepinephrine has a higher a ffinity than epinephrine in the beta(1)-adrenergic receptor subtype, w hile the specificity is reversed in the beta(2)- and beta(3)-adrenergi c receptor subtypes. This new method offers much potential in the deve lopment of new force fields, particularly those involving polarization through induced dipoles, because only fitted charges and dipoles are required to reproduce quantitatively electrostatic interactions.