Partial molecular alignment via local structure analysis

Molecular alignment remains as one of the most problematic aspects of molec ular design. A technique is introduced that facilitates the alignment of a range of structures that could not be handled easily using existing alignme nt procedures. The flexibility of the method is illustrated with a series o f test sets, First, an alignment is performed on a series of molecules from a typical 3D-quantitative structure-activity relationship data set. The re sults of this test show the technique to outperform many existing alignment methodologies based upon the optimization of molecular similarity or molec ular overlaps. This test set is then extended to consider the alignment of more structurally diverse inhibitors of HIV-1 reverse transcriptase and HIV -1 protease. Finally, in the most challenging test, a large protein-based i nhibitor is matched with a small-molecule mimic. It is believed that the ex istence of such a versatile alignment technique will prove invaluable in th e fields of molecular design and chemical information handling.