Consensus bond-charge increments fitted to electrostatic potential or field of many compounds: Application to MMFF94 training set

Ž . ABSTRACT: Bond-charge increments BCIs are additive parameters used to assign atomic charges for the MMFF force field. BCI parameters are classified parsimoniously according to two atom types and the bond order. We show how BCIs may be fitted rapidly by linear least squares to the calculated ab initio Ž . electrostatic potential ESP or to the electrostatic field. When applied simultaneously to a set of compounds or conformations, the method yields consensus values of the BCIs. The method can also derive conventional ‘‘ESP-fit’’ atomic charges with improved numerical stability. The method may be generalized to determine atom multipoles, multicenter charge templates, or electronegativities, but not polarizability or hardness. We determine 65 Ž . potential-derived PD BCI parameters, which are classified as in MMFF, by fitting the 6-31G* ESP or the electrostatic field of the 45 compounds in the original MMFF94 training set. We compare the consensus BCIs with classified BCIs that were fit to each molecule individually and with ‘‘unique-bond’’ BCIs Ž . ESP-derived atom charges . Consensus BCIs give a satisfactory representation for about half of the structures and are robust to the adjustment of the alkyl CH bond increment to the zero value employed in MMFF94. We highlight problems at three levels: Point approximation: the potential near lone pairs on sulfur and to some extent nitrogen cannot be represented just by atom charges. Bond classification: BCIs classified according to MMFF atom types cannot represent all