title: Comparison of binary and 2D QSAR analyses using inhibitors of human carbonic anhydrase II as a test case.
abstract: Binary and conventional 2D QSAR have been derived for a set of carbonic anhydrase II (CA II) inhibitors. An overall predictive accuracy of 94% was obtained by binary QSAR and of 84% by 2D QSAR model. For both models, preferred molecular descriptor sets were identified, which were overlapping but not identical. Both binary and 2D QSAR captured important molecular features of CA II inhibitors, notably the presence of a sulfonamido group, which is critical for binding, but also hydrophobicity. Promising results were obtained when the derived QSAR models were used to test a set of CA II inhibitors not included in the training set. In binary QSAR, previously unobserved boundary effects were detected both in the analysis of known inhibitors and when screening a large combinatorial library for putative inhibitors. The complementary use of binary and conventional 2D QSAR is thought to increase the accuracy of the lead discovery process by QSAR techniques.
authors.affiliation: Computational Chemistry and Informatics, MDS Panlabs, Bothell, WA 98011, USA.
authors.forename: H
authors.initials: H
authors.lastname: Gao
authors.forename: J
authors.initials: J
authors.lastname: Bajorath
mesh_terms: D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism; D016208:Databases, Factual; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D015233:Models, Statistical; D008968:Molecular Conformation; D015394:Molecular Structure; D015203:Reproducibility of Results; D013329:Structure-Activity Relationship
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D002256:Carbonic Anhydrases