title: 2D QSAR consensus prediction for high-throughput virtual screening. An application to COX-2 inhibition modeling and screening of the NCI database.
abstract: Using classification (SOM, LVQ, Binary, Decision Tree) and regression algorithms (PLS, BRANN, k-NN, Linear), this paper details the building of eight 2D-QSAR models from a 266 COX-2 inhibitor training set. The predictive performances of these eight models were subsequently compared using an 88 COX-2 inhibitor test set. Each ligand is described by 52 2D descriptors expressed as van der Waals Surface Areas (P_VSA) and its COX-2 binding IC50. One of our best predictive models is the neural network model (BRANN), which is able to select a subset, from the 88 ligand test set, that contains 94% COX-2 active inhibitors (pIC50>7.5) and detects 71% of all the actives. We then introduce a QSAR consensus prediction protocol that is shown to be more predictive than any single QSAR model: our C3 consensus approach is able to select a subset from the 88 ligand test set that contains 94% active inhibitors and 83% of all the actives. The 2D QSAR consensus protocol was finally applied to the high-throughput virtual screening of the NCI database, containing 193,477 organic compounds.
authors.affiliation: Institut de Chimie Organique et Analytique, UMR 6005, Université d'Orléans, BP 6759, F-45067 Orléans Cedex 2, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Baurin
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Mozziconacci
authors.forename: Eric
authors.initials: E
authors.lastname: Arnoult
authors.forename: Philippe
authors.initials: P
authors.lastname: Chavatte
authors.forename: Christophe
authors.initials: C
authors.lastname: Marot
authors.forename: Luc
authors.initials: L
authors.lastname: Morin-Allory
mesh_terms: D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D003628:Database Management Systems; D007527:Isoenzymes / Q000187:drug effects*; D009316:National Institutes of Health (U.S.); D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects*; D021281:Quantitative Structure-Activity Relationship; D014481:United States
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases