Fast, efficient generation of high-quality atomic Charges. AM1-BCC model: I. Method

The AM1-BCC method quickly and efficiently generates high-quality atomic ch arges for use in condensed-phase simulations. The underlying features of th e electron distribution including formal charge and delocalization are firs t captured by AM1 atomic charges for the individual molecule. Bond charge c orrections (BCCs), which have been parameterized against the HF/6-31G* elec trostatic potential (ESP) of a training set of compounds containing relevan t functional groups, are then added using a formalism identical to the cons ensus BCI (bond charge increment) approach. As a proof of the concept, we f it BCCs simultaneously to 45 compounds including O-, N-, and S-containing f unctionalities, aromatics, and hetoroaromatics, using only 41 BCC parameter s. AM1-BCC yields charge sets of comparable quality to HF/6-31G* ESP-derive d charges in a fraction of the time while reducing instabilities in the ato mic charges compared to direct ESP-fit methods. We then apply the BCC param eters to a small "test set" consisting of aspirin, D-glucose, and eryodicty ol; the AM1-BCC model again provides atomic charges of quality comparable w ith HF/6-31G* RESP charges, as judged by an increase of only 0.01 to 0.02 a tomic units in the root-mean-square (RMS) error in ESP. Based on these enco uraging results, we intend to parameterize the AM1-BCC model to provide a c onsistent charge model for any organic or biological molecule. (C) 2000 Joh n Wiley & Sons, Inc.