CONFORMATIONAL DEPENDENCE OF ELECTROSTATIC POTENTIAL-DERIVED CHARGES - STUDIES OF THE FITTING PROCEDURE

Atomic monopole ''point charges'' are routinely determined through a l east squares fit to molecular electrostatic potentials potential-deri ved (PD) charges). Previously, it has been shown that these charges va ry with variation in molecular conformation. Also, it has been observe d that these swings in charges are highly correlated between neighbori ng atoms. Here, we examine the least squares variance-covariance data matrices for a set of data in the literature and find further indicati ons of high colinearity within the data. These colinearities effective ly reduce the dimensionality of the data to a value well below the num ber of atoms in the molecules. This suggests that the data is not of s ufficient dimensionality to support calculation of the charges for all of the atoms in a statistically significant way. We experiment with f ixing the charges of atoms whose PD charges reflect large errors in th e fit. The resulting estimates of fit of the remaining charges are lit tle degraded from the estimates of fit when the charges of all of the atoms are fit. In addition, the charges that are fit take what would b e considered more reasonable and ''chemically intuitive'' values, ofte n of smaller magnitude. Although most of the free charges continue to vary with molecular conformation, their range is no larger than when a ll charges were fit and, in some cases, the ranges of the charges for the fit atoms is actually reduced over those that are found when all o f the atoms take part in the fitting procedure. The errors of fit are lower and the unconstrained charges appear more reasonable when more c hemically ''reasonable'' charges are used for the fixed values. This s uggests that in many cases charges are transferable between molecules. Further, it shows a way to justifiably reduce the large fluctuations in PD charges that occur with variations in conformation.