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.