title: Evaluation of a novel virtual screening strategy using receptor decoy binding sites.
abstract: Virtual screening is used in biomedical research to predict the binding affinity of a large set of small organic molecules to protein receptor targets. This report shows the development and evaluation of a novel yet straightforward attempt to improve this ranking in receptor-based molecular docking using a receptor-decoy strategy. This strategy includes defining a decoy binding site on the receptor and adjusting the ranking of the true binding-site virtual screen based on the decoy-site screen. The results show that by docking against a receptor-decoy site with Autodock Vina, improved Receiver Operator Characteristic Enrichment (ROCE) was achieved for 5 out of fifteen receptor targets investigated, when up to 15 % of a decoy site rank list was considered. No improved enrichment was seen for 7 targets, while for 3 targets the ROCE was reduced. The extent to which this strategy can effectively improve ligand prediction is dependent on the target receptor investigated.
authors.affiliation: Department of Biological and Environmental Sciences, University of Hertfordshire, College Lane, Hatfield, AL10 9AB, UK.
authors.forename: Hershna
authors.initials: H
authors.lastname: Patel
authors.affiliation: Department of Biological and Environmental Sciences, University of Hertfordshire, College Lane, Hatfield, AL10 9AB, UK. a.kukol@herts.ac.uk.
authors.forename: Andreas
authors.identifier: http://orcid.org/0000-0002-8859-010X
authors.initials: A
authors.lastname: Kukol
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D001665:Binding Sites; D004353:Drug Evaluation, Preclinical; D008958:Models, Molecular; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: D011956:Receptors, Cell Surface; D000110:Acetylcholinesterase
keywords: Adjusted ranking; Autodock Vina; Docking; Enrichment; Receptor-decoy; Virtual screening