M. Bradley et al., DEDUCING MOLECULAR SIMILARITY USING VORONOI BINDING-SITES, Journal of chemical information and computer sciences, 33(5), 1993, pp. 750-755
We have devised a new measure of molecular similarity with respect to
given simple partitions of space into regions. The similarity is deter
mined by numerical integration of the difference in the optimal intera
ction between the two molecules and the regions over a large range of
interaction parameter values. Compounds differing in empirical formula
are differentiated by a single infinite region; cis/trans or ortho/me
ta/para isomers are distinguishable by two adjacent regions that are h
alf-spaces; and stereoisomers require five regions. This can be viewed
as a natural classification of isomers. The concept can also be appli
ed to drug binding studies to determine which molecules may bind alike
in a given biological receptor and to elucidate a necessary starting
geometry when a binding site is modeled for inhibitors whose experimen
tal binding energies are different.