HierS: Hierarchical scaffold clustering


Steven J. Wilkens, Jeff J. Janes, and Andrew I. Su. Computational Discovery, Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, C115, San Diego, CA 92121
An exhaustive ring-based algorithm has been developed to provide an intuitive approach to compound clustering. The recursive algorithm rapidly identifies all ring-delimited substructures within a compound. Molecules are grouped by shared ring substructures (scaffolds) so that common scaffolds obtain higher membership and greater importance. Once all of the scaffolds are identified, hierarchical structural relationships are established. The complex network of hierarchical relationships is then utilized to navigate compounds in a structurally directed fashion. The utility of this approach is demonstrated by providing readily interpretable model for chemical diversity in different compound sets. In addition, a web-based application has been developed which incorporates this algorithm in order to allow for the interactive analysis of the diverse sets of compounds that are produced from high-throughput screening. Biological data is coupled to scaffolds by the inclusion of activity histograms, which indicate how the compounds in each scaffold class performed in other screens.

General Papers
2:30 PM-5:00 PM, Thursday, August 26, 2004 Pennsylvania Convention Center -- 110A&B, Oral

Division of Chemical Information

The 228th ACS National Meeting, in Philadelphia, PA, August 22-26, 2004