title: Finding discriminating structural features by reassembling common building blocks.
abstract: We present a new method for constructing discriminating substructures by reassembling common medicinal chemistry building blocks. The algorithm can be parametrized to meet differing objectives: (1) to build features that discriminate for biological activity in a local structural neighborhood, (2) to build scaffolds for R-group analysis, (3) to construct cluster signatures that discriminate for membership in the cluster and provide a graphical representation for its members, and (4) to identify substructures that characterize major classes in a heterogeneous compound set. We illustrated the results of the algorithm on a literature dataset is of 118 compounds with in vitro inhibition data against recombinant human protein tyrosine phosphatase 1B (PTP-1B).
authors.affiliation: Leadscope, Inc., 1245 Kinnear Road, Columbus, Ohio 43212, USA.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Cross
authors.forename: Glenn
authors.initials: G
authors.lastname: Myatt
authors.forename: Chihae
authors.initials: C
authors.lastname: Yang
authors.forename: Michael A
authors.initials: MA
authors.lastname: Fligner
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Verducci
authors.forename: Paul E
authors.initials: PE
authors.lastname: Blower
mesh_terms: D000465:Algorithms; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry; D006801:Humans; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship; D011994:Recombinant Proteins / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases