A method is presented for flexibly aligning small molecules. The method acc
epts a collection of small molecules with 3D coordinates as input and compu
tes a collection of alignments. Each alignment is given a score, which quan
tifies the quality of the alignment both in terms of internal strain and ov
erlap of molecular features. The results of several computational experimen
ts on pairs of compounds with known binding conformations are used to syste
matically and objectively tune the parameters for the method. The results i
ndicate the method's utility for the elucidation of pharmacophores and comp
arative field analysis.