title: Extensive consensus docking evaluation for ligand pose prediction and virtual screening studies.
abstract: Molecular docking strategies are one of the most widely used techniques for predicting the binding mode of a ligand and for obtaining new hits in virtual screening studies. In order to improve the accuracy of this approach, we tested the reliability of applying a consensus docking protocol by combining ten different docking procedures. The analysis was carried out in terms of consensus cross-docking and by using an enriched database. The results highlight that from a qualitative point of view consensus docking is able to predict the ligand binding pose better than the single docking programs and is also able to give hints concerning the reliability of the docking pose. With regard to the virtual screening studies, consensus docking was evaluated for three different targets of the Directory of Useful Decoys (DUD), and the obtained results suggest that this approach performs as well as the best available methods found in the literature, therefore supporting the idea that this procedure can be profitably applied for the identification of new hits.
authors.affiliation: Department of Pharmacy, University of Pisa , 56126 Pisa, Italy.
authors.forename: Tiziano
authors.initials: T
authors.lastname: Tuccinardi
authors.forename: Giulio
authors.initials: G
authors.lastname: Poli
authors.forename: Veronica
authors.initials: V
authors.lastname: Romboli
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
authors.forename: Adriano
authors.initials: A
authors.lastname: Martinelli
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D001665:Binding Sites; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000737:chemistry*; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding; D008024:Ligands; D008968:Molecular Conformation; D062105:Molecular Docking Simulation / Q000379:methods*; D011485:Protein Binding; D054852:Small Molecule Libraries / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D014584:User-Computer Interface
chemical_list: D004791:Enzyme Inhibitors; D047628:Estrogen Receptor alpha; D008024:Ligands; D054852:Small Molecule Libraries; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human