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Article: Virtual screening to enrich hit lists from high-throughput screening: A case study on small-molecule inhibitors of angiogenin

TitleVirtual screening to enrich hit lists from high-throughput screening: A case study on small-molecule inhibitors of angiogenin
Authors
Issue Date2003
Citation
Proteins: Structure, Function And Genetics, 2003, v. 50 n. 1, p. 81-93 How to Cite?
Abstract"Hit lists" generated by high-throughput screening (HTS) typically contain a large percentage of false positives, making follow-up assays necessary to distinguish active from inactive substances. Here we present a method for improving the accuracy of HTS hit lists by computationally based virtual screening (VS) of the corresponding chemical libraries and selecting hits by HTS/VS consensus. This approach was applied in a case study on the target-enzyme angiogenin, a potent inducer of angiogenesis. In conjunction with HTS of the National Cancer Institute Diversity Set and ChemBridge DIVERSet E (∼18,000 compounds total), VS was performed with two flexible library docking/scoring methods, DockVision/Ludi and GOLD. Analysis of the results reveals that dramatic enrichment of the HTS hit rate can be achieved by selecting compounds in consensus with one or both of the VS functions. For example, HTS hits ranked in the top 2% by GOLD included 42% of the true hits, but only 8% of the false positives; this represents a sixfold enrichment over the HTS hit rate. Notably, the HTS/VS method was effective in selecting out inhibitors with midmicromolar dissociation constants typical of leads commonly obtained in primary screens. © 2002 Wiley-Liss, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/157352
ISSN
2015 Impact Factor: 2.499
2015 SCImago Journal Rankings: 1.383
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorJenkins, JLen_US
dc.contributor.authorKao, RYTen_US
dc.contributor.authorShapiro, Ren_US
dc.date.accessioned2012-08-08T08:49:09Z-
dc.date.available2012-08-08T08:49:09Z-
dc.date.issued2003en_US
dc.identifier.citationProteins: Structure, Function And Genetics, 2003, v. 50 n. 1, p. 81-93en_US
dc.identifier.issn0887-3585en_US
dc.identifier.urihttp://hdl.handle.net/10722/157352-
dc.description.abstract"Hit lists" generated by high-throughput screening (HTS) typically contain a large percentage of false positives, making follow-up assays necessary to distinguish active from inactive substances. Here we present a method for improving the accuracy of HTS hit lists by computationally based virtual screening (VS) of the corresponding chemical libraries and selecting hits by HTS/VS consensus. This approach was applied in a case study on the target-enzyme angiogenin, a potent inducer of angiogenesis. In conjunction with HTS of the National Cancer Institute Diversity Set and ChemBridge DIVERSet E (∼18,000 compounds total), VS was performed with two flexible library docking/scoring methods, DockVision/Ludi and GOLD. Analysis of the results reveals that dramatic enrichment of the HTS hit rate can be achieved by selecting compounds in consensus with one or both of the VS functions. For example, HTS hits ranked in the top 2% by GOLD included 42% of the true hits, but only 8% of the false positives; this represents a sixfold enrichment over the HTS hit rate. Notably, the HTS/VS method was effective in selecting out inhibitors with midmicromolar dissociation constants typical of leads commonly obtained in primary screens. © 2002 Wiley-Liss, Inc.en_US
dc.languageengen_US
dc.relation.ispartofProteins: Structure, Function and Geneticsen_US
dc.subject.meshBinding Sitesen_US
dc.subject.meshComputational Biology - Methodsen_US
dc.subject.meshComputer Simulationen_US
dc.subject.meshDatabases, Factualen_US
dc.subject.meshEnzyme Inhibitors - Analysis - Chemistry - Metabolismen_US
dc.subject.meshLigandsen_US
dc.subject.meshModels, Molecularen_US
dc.subject.meshReproducibility Of Resultsen_US
dc.subject.meshRibonuclease, Pancreatic - Antagonists & Inhibitors - Chemistry - Metabolismen_US
dc.titleVirtual screening to enrich hit lists from high-throughput screening: A case study on small-molecule inhibitors of angiogeninen_US
dc.typeArticleen_US
dc.identifier.emailKao, RYT:rytkao@hkucc.hku.hken_US
dc.identifier.authorityKao, RYT=rp00481en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1002/prot.10270en_US
dc.identifier.pmid12471601en_US
dc.identifier.scopuseid_2-s2.0-0037235881en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0037235881&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume50en_US
dc.identifier.issue1en_US
dc.identifier.spage81en_US
dc.identifier.epage93en_US
dc.identifier.isiWOS:000180131100008-
dc.identifier.scopusauthoridJenkins, JL=7402867712en_US
dc.identifier.scopusauthoridKao, RYT=7101675499en_US
dc.identifier.scopusauthoridShapiro, R=7403082810en_US
dc.identifier.citeulike478680-

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