| Abstract
| - An exhaustive ring-based algorithm, HierS, has been developed in order to provide an intuitiveapproach to compound clustering for analyzing high-throughput screening results. The recursivealgorithm rapidly identifies all possible ring-delimited substructures within a set of compounds.Molecules are grouped by shared ring substructures (scaffolds) so that common scaffolds obtainhigher membership. Once all of the scaffolds for a set of compounds are identified, thehierarchical structural relationships between the scaffold structures are established. Thecomplex network of hierarchical relationships is then utilized to navigate compounds in astructurally directed fashion. When the scaffold hierarchy is traversed, over-representedstructural features can be rapidly identified so that excess compounds that contain them canbe removed without significantly impacting the structural diversity landscape of the compoundset. Furthermore, the removed compounds can provide the opportunity to follow-up on activecompounds that had previously been discarded because of practical limitations on follow-upcapacity. A Web-based interface has been developed that incorporates this algorithm in orderto allow for an interactive analysis. In addition, biological data are coupled to scaffolds by theinclusion of activity histograms, which indicate how the compounds in each scaffold classperformed in previous high-throughput screening campaigns.
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