A novel method of aligning molecules by local surface shape similarity

A novel shape-based method has been developed for overlaying a series of mo lecule surfaces into a common reference frame. The surfaces are represented by a set of circular patches of approximately constant curvature. Two mole cules are overlaid using a clique-detection algorithm to find a set of patc hes in the two surfaces that correspond, and overlaying the molecules so th at the similar patches on the two surfaces are coincident. The method is th us able to detect areas of local, rather than global, similarity. A consens us overlay for a group of molecules is performed by examining the scores of all pairwise overlays and performing a set of overlays with the highest sc ores. The utility of the method has been examined by comparing the overlaid and experimental configurations of 4 sets of molecules for which there are X-ray crystal structures of the molecules bound to a protein active site. Results for the overlays are generally encouraging. Of particular note is t he correct prediction of the 'reverse orientation' for ligands binding to h uman rhinovirus coat protein HRV14.