title: Importance of the pharmacological profile of the bound ligand in enrichment on nuclear receptors: toward the use of experimentally validated decoy ligands.
abstract: The evaluation of virtual ligand screening methods is of major importance to ensure their reliability. Taking into account the agonist/antagonist pharmacological profile should improve the quality of the benchmarking data sets since ligand binding can induce conformational changes in the nuclear receptor structure and such changes may vary according to the agonist/antagonist ligand profile. We indeed found that splitting the agonist and antagonist ligands into two separate data sets for a given nuclear receptor target significantly enhances the quality of the evaluation. The pharmacological profile of the ligand bound in the binding site of the target structure was also found to be an additional critical parameter. We also illustrate that active compound data sets for a given pharmacological activity can be used as a set of experimentally validated decoy ligands for another pharmacological activity to ensure a reliable and challenging evaluation of virtual screening methods.
authors.affiliation: Laboratoire Génomique, Bioinformatique et Applications, EA 4627, Conservatoire National des Arts et Métiers , 292 rue Saint Martin, 75003 Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Lagarde
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Zagury
authors.forename: Matthieu
authors.initials: M
authors.lastname: Montes
mesh_terms: D019985:Benchmarking; D001665:Binding Sites; D062126:Databases, Chemical; D030562:Databases, Protein; D055808:Drug Discovery; D057166:High-Throughput Screening Assays; D006801:Humans; D008024:Ligands; D008968:Molecular Conformation; D011485:Protein Binding; D012372:ROC Curve; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000737:chemistry; D015203:Reproducibility of Results; D054852:Small Molecule Libraries / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014584:User-Computer Interface
chemical_list: D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D054852:Small Molecule Libraries