Finding discriminating structural features by reassembling common building blocks.
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).
Cross
Kevin P
KP
Leadscope, Inc., 1245 Kinnear Road, Columbus, Ohio 43212, USA.
Myatt
Glenn
G
Yang
Chihae
C
Fligner
Michael A
MA
Verducci
Joseph S
JS
Blower
Paul E
PE
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
D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases