Benchmarking Sets for Molecular Docking
Ligand enrichment among top-ranking hits is a key metric of molecular docking. To avoid bias, decoys should resemble ligands physically, so that enrichment is not simply a separation of gross features, yet be chemically distinct from them, so that they are unlikely to be binders. We have assembled a...
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| Veröffentlicht in: | Journal of medicinal chemistry 2006-11, Vol.49 (23), p.6789-6801 |
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| container_title | Journal of medicinal chemistry |
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| creator | Huang, Niu Shoichet, Brian K Irwin, John J |
| description | Ligand enrichment among top-ranking hits is a key metric of molecular docking. To avoid bias, decoys should resemble ligands physically, so that enrichment is not simply a separation of gross features, yet be chemically distinct from them, so that they are unlikely to be binders. We have assembled a directory of useful decoys (DUD), with 2950 ligands for 40 different targets. Every ligand has 36 decoy molecules that are physically similar but topologically distinct, leading to a database of 98 266 compounds. For most targets, enrichment was at least half a log better with uncorrected databases such as the MDDR than with DUD, evidence of bias in the former. These calculations also allowed 40 × 40 cross-docking, where the enrichments of each ligand set could be compared for all 40 targets, enabling a specificity metric for the docking screens. DUD is freely available online as a benchmarking set for docking at http://blaster.docking.org/dud/. |
| doi_str_mv | 10.1021/jm0608356 |
| format | Article |
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Drug treatments ; Protein Binding ; Protein Conformation ; Proteins - chemistry ; Quantitative Structure-Activity Relationship ; Receptors, Estrogen - antagonists & inhibitors ; Receptors, Estrogen - chemistry ; Thymidine Kinase - chemistry</subject><ispartof>Journal of medicinal chemistry, 2006-11, Vol.49 (23), p.6789-6801</ispartof><rights>Copyright © 2006 American Chemical Society</rights><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a471t-ddc920fc833e0c2446edf7c9dc9b60f087477831aab4678e0b9e91d2e11c495e3</citedby><cites>FETCH-LOGICAL-a471t-ddc920fc833e0c2446edf7c9dc9b60f087477831aab4678e0b9e91d2e11c495e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jm0608356$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm0608356$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>230,314,780,784,885,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18270983$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17154509$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Huang, Niu</creatorcontrib><creatorcontrib>Shoichet, Brian K</creatorcontrib><creatorcontrib>Irwin, John J</creatorcontrib><title>Benchmarking Sets for Molecular Docking</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>Ligand enrichment among top-ranking hits is a key metric of molecular docking. To avoid bias, decoys should resemble ligands physically, so that enrichment is not simply a separation of gross features, yet be chemically distinct from them, so that they are unlikely to be binders. We have assembled a directory of useful decoys (DUD), with 2950 ligands for 40 different targets. Every ligand has 36 decoy molecules that are physically similar but topologically distinct, leading to a database of 98 266 compounds. For most targets, enrichment was at least half a log better with uncorrected databases such as the MDDR than with DUD, evidence of bias in the former. These calculations also allowed 40 × 40 cross-docking, where the enrichments of each ligand set could be compared for all 40 targets, enabling a specificity metric for the docking screens. DUD is freely available online as a benchmarking set for docking at http://blaster.docking.org/dud/.</description><subject>Adenosine Deaminase - chemistry</subject><subject>Aldehyde Reductase - chemistry</subject><subject>Binding Sites</subject><subject>Biological and medical sciences</subject><subject>Databases, Factual</subject><subject>Drug Design</subject><subject>Inhibins - chemistry</subject><subject>Ligands</subject><subject>Medical sciences</subject><subject>Miscellaneous</subject><subject>Models, Molecular</subject><subject>p38 Mitogen-Activated Protein Kinases - chemistry</subject><subject>Pharmaceutical Preparations - chemistry</subject><subject>Pharmacology. Drug treatments</subject><subject>Protein Binding</subject><subject>Protein Conformation</subject><subject>Proteins - chemistry</subject><subject>Quantitative Structure-Activity Relationship</subject><subject>Receptors, Estrogen - antagonists & inhibitors</subject><subject>Receptors, Estrogen - chemistry</subject><subject>Thymidine Kinase - chemistry</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkE1PGzEURS0EKiHtgj9QZdOiLoY-f4zt2SBRaAEVBCIgKjaW43kDEyZjsGcq-PcYJUpaiZUl36P7rg4h2xR2KTD6fToDCZrnco0MaM4gExrEOhkAMJYxyfgm2YpxCgCcMv6BbFJFc5FDMSA7P7B19zMbHur2bjTGLo4qH0ZnvkHXNzaMDr17iz6Sjco2ET8t3iG5_vXz6uA4Oz0_OjnYP82sULTLytIVDCqnOUdwTAiJZaVckb4nEirQSiilObV2IqTSCJMCC1oypNSJIkc-JHvz3sd-MsPSYdsF25jHUKeNL8bb2vyftPW9ufN_DefpJlWp4OuiIPinHmNnZnV02DS2Rd9HIzXjBdUygd_moAs-xoDV8ggF86bVLLUm9vO_q1bkwmMCviwAG51tqmBbV8cVp5mCIg0ckmzO1bHD52We9BupuMrN1cXY3Nyqy_HvP8zcrnqti2bq-9Am-e8MfAXmzJn8</recordid><startdate>20061116</startdate><enddate>20061116</enddate><creator>Huang, Niu</creator><creator>Shoichet, Brian K</creator><creator>Irwin, John J</creator><general>American Chemical Society</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20061116</creationdate><title>Benchmarking Sets for Molecular Docking</title><author>Huang, Niu ; Shoichet, Brian K ; Irwin, John J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a471t-ddc920fc833e0c2446edf7c9dc9b60f087477831aab4678e0b9e91d2e11c495e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adenosine Deaminase - chemistry</topic><topic>Aldehyde Reductase - chemistry</topic><topic>Binding Sites</topic><topic>Biological and medical sciences</topic><topic>Databases, Factual</topic><topic>Drug Design</topic><topic>Inhibins - chemistry</topic><topic>Ligands</topic><topic>Medical sciences</topic><topic>Miscellaneous</topic><topic>Models, Molecular</topic><topic>p38 Mitogen-Activated Protein Kinases - chemistry</topic><topic>Pharmaceutical Preparations - chemistry</topic><topic>Pharmacology. Drug treatments</topic><topic>Protein Binding</topic><topic>Protein Conformation</topic><topic>Proteins - chemistry</topic><topic>Quantitative Structure-Activity Relationship</topic><topic>Receptors, Estrogen - antagonists & inhibitors</topic><topic>Receptors, Estrogen - chemistry</topic><topic>Thymidine Kinase - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Huang, Niu</creatorcontrib><creatorcontrib>Shoichet, Brian K</creatorcontrib><creatorcontrib>Irwin, John J</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huang, Niu</au><au>Shoichet, Brian K</au><au>Irwin, John J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Benchmarking Sets for Molecular Docking</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>2006-11-16</date><risdate>2006</risdate><volume>49</volume><issue>23</issue><spage>6789</spage><epage>6801</epage><pages>6789-6801</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>Ligand enrichment among top-ranking hits is a key metric of molecular docking. To avoid bias, decoys should resemble ligands physically, so that enrichment is not simply a separation of gross features, yet be chemically distinct from them, so that they are unlikely to be binders. We have assembled a directory of useful decoys (DUD), with 2950 ligands for 40 different targets. Every ligand has 36 decoy molecules that are physically similar but topologically distinct, leading to a database of 98 266 compounds. For most targets, enrichment was at least half a log better with uncorrected databases such as the MDDR than with DUD, evidence of bias in the former. These calculations also allowed 40 × 40 cross-docking, where the enrichments of each ligand set could be compared for all 40 targets, enabling a specificity metric for the docking screens. DUD is freely available online as a benchmarking set for docking at http://blaster.docking.org/dud/.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>17154509</pmid><doi>10.1021/jm0608356</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of medicinal chemistry, 2006-11, Vol.49 (23), p.6789-6801 |
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| source | MEDLINE; American Chemical Society Journals |
| subjects | Adenosine Deaminase - chemistry Aldehyde Reductase - chemistry Binding Sites Biological and medical sciences Databases, Factual Drug Design Inhibins - chemistry Ligands Medical sciences Miscellaneous Models, Molecular p38 Mitogen-Activated Protein Kinases - chemistry Pharmaceutical Preparations - chemistry Pharmacology. Drug treatments Protein Binding Protein Conformation Proteins - chemistry Quantitative Structure-Activity Relationship Receptors, Estrogen - antagonists & inhibitors Receptors, Estrogen - chemistry Thymidine Kinase - chemistry |
| title | Benchmarking Sets for Molecular Docking |
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