Estimating binding affinities by docking/scoring methods using variable protonation states
To investigate the effects of multiple protonation states on protein–ligand recognition, we generated alternative protonation states for selected titratable groups of ligands and receptors. The selection of states was based on the predicted pK a of the unbound receptor and ligand and the proximity o...
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| Veröffentlicht in: | Proteins, structure, function, and bioinformatics structure, function, and bioinformatics, 2011-01, Vol.79 (1), p.304-314 |
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| creator | Park, Min-Sun Gao, Cen Stern, Harry A. |
| description | To investigate the effects of multiple protonation states on protein–ligand recognition, we generated alternative protonation states for selected titratable groups of ligands and receptors. The selection of states was based on the predicted pK
a of the unbound receptor and ligand and the proximity of titratable groups of the receptor to the binding site. Various ligand tautomer states were also considered. An independent docking calculation was run for each state. Several protocols were examined: using an ensemble of all generated states of ligand and receptor, using only the most probable state of the unbound ligand/receptor, and using only the state giving the most favorable docking score. The accuracies of these approaches were compared, using a set of 176 protein–ligand complexes (15 receptors) for which crystal structures and measured binding affinities are available. The best agreement with experiment was obtained when ligand poses from experimental crystal structures were used. For 9 of 15 receptors, using an ensemble of all generated protonation states of the ligand and receptor gave the best correlation between calculated and measured affinities. Proteins 2010. © 2010 Wiley‐Liss, Inc. |
| doi_str_mv | 10.1002/prot.22883 |
| format | Article |
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a of the unbound receptor and ligand and the proximity of titratable groups of the receptor to the binding site. Various ligand tautomer states were also considered. An independent docking calculation was run for each state. Several protocols were examined: using an ensemble of all generated states of ligand and receptor, using only the most probable state of the unbound ligand/receptor, and using only the state giving the most favorable docking score. The accuracies of these approaches were compared, using a set of 176 protein–ligand complexes (15 receptors) for which crystal structures and measured binding affinities are available. The best agreement with experiment was obtained when ligand poses from experimental crystal structures were used. For 9 of 15 receptors, using an ensemble of all generated protonation states of the ligand and receptor gave the best correlation between calculated and measured affinities. Proteins 2010. © 2010 Wiley‐Liss, Inc.</description><identifier>ISSN: 0887-3585</identifier><identifier>EISSN: 1097-0134</identifier><identifier>DOI: 10.1002/prot.22883</identifier><identifier>PMID: 21058298</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>binding pose ; Computer Simulation ; docking ; Hydrogen-Ion Concentration ; Ligands ; Models, Molecular ; Protein Binding ; Protein Structure, Tertiary ; protein-ligand binding affinity ; protonation state ; Receptors, Cytoplasmic and Nuclear - chemistry ; scoring function</subject><ispartof>Proteins, structure, function, and bioinformatics, 2011-01, Vol.79 (1), p.304-314</ispartof><rights>Copyright © 2010 Wiley‐Liss, Inc.</rights><rights>2010 Wiley-Liss, Inc.</rights><rights>Copyright © 2010 Wiley-Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4273-8427e27f291db73a153d697eee53b98d7f3ed8e3a4b48ec8a910baaf16e59b143</citedby><cites>FETCH-LOGICAL-c4273-8427e27f291db73a153d697eee53b98d7f3ed8e3a4b48ec8a910baaf16e59b143</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fprot.22883$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fprot.22883$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21058298$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Park, Min-Sun</creatorcontrib><creatorcontrib>Gao, Cen</creatorcontrib><creatorcontrib>Stern, Harry A.</creatorcontrib><title>Estimating binding affinities by docking/scoring methods using variable protonation states</title><title>Proteins, structure, function, and bioinformatics</title><addtitle>Proteins</addtitle><description>To investigate the effects of multiple protonation states on protein–ligand recognition, we generated alternative protonation states for selected titratable groups of ligands and receptors. The selection of states was based on the predicted pK
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Proteins 2010. © 2010 Wiley‐Liss, Inc.</description><subject>binding pose</subject><subject>Computer Simulation</subject><subject>docking</subject><subject>Hydrogen-Ion Concentration</subject><subject>Ligands</subject><subject>Models, Molecular</subject><subject>Protein Binding</subject><subject>Protein Structure, Tertiary</subject><subject>protein-ligand binding affinity</subject><subject>protonation state</subject><subject>Receptors, Cytoplasmic and Nuclear - chemistry</subject><subject>scoring function</subject><issn>0887-3585</issn><issn>1097-0134</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUtP5SAUgIlxotfHxh9gmrgYM0mVRyl0qcbHTHzFaEzcEGhPFe0tDlD1_vuhc9WFC1lwAnzny-EchDYI3iEY091n7-IOpVKyBTQhuBI5JqxYRBMspcgZl3wZrYTwiDEuK1YuoWVKMJe0khN0dxiinepo-_vM2L4Zo25b29toIWRmljWufkq3u6F2fnydQnxwTciGMJ5etLfadJCNRbg-iVyfhagjhDX0o9VdgPX3uIpujg6vD07y04vj3wd7p3ldUMFymXagoqUVaYxgmnDWlJUAAM5MJRvRMmgkMF2YQkItdUWw0bolJfDKkIKtop9zbyrh7wAhqqkNNXSd7sENQUnC08IlTeT2t2SSFZhyKXBCt76gj27wffqHIqnTvOQFHYW_5lTtXQgeWvXsUzf9TBGsxtmosS3q_2wSvPmuHMwUmk_0YxgJIHPg1XYw-0alLq8urj-k-TzHhghvnznaP6lSMMHV7fmxuqRn4uTPFVP77B-OPalr</recordid><startdate>201101</startdate><enddate>201101</enddate><creator>Park, Min-Sun</creator><creator>Gao, Cen</creator><creator>Stern, Harry A.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</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>7QL</scope><scope>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201101</creationdate><title>Estimating binding affinities by docking/scoring methods using variable protonation states</title><author>Park, Min-Sun ; Gao, Cen ; Stern, Harry A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4273-8427e27f291db73a153d697eee53b98d7f3ed8e3a4b48ec8a910baaf16e59b143</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>binding pose</topic><topic>Computer Simulation</topic><topic>docking</topic><topic>Hydrogen-Ion Concentration</topic><topic>Ligands</topic><topic>Models, Molecular</topic><topic>Protein Binding</topic><topic>Protein Structure, Tertiary</topic><topic>protein-ligand binding affinity</topic><topic>protonation state</topic><topic>Receptors, Cytoplasmic and Nuclear - chemistry</topic><topic>scoring function</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Park, Min-Sun</creatorcontrib><creatorcontrib>Gao, Cen</creatorcontrib><creatorcontrib>Stern, Harry A.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Proteins, structure, function, and bioinformatics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Park, Min-Sun</au><au>Gao, Cen</au><au>Stern, Harry A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Estimating binding affinities by docking/scoring methods using variable protonation states</atitle><jtitle>Proteins, structure, function, and bioinformatics</jtitle><addtitle>Proteins</addtitle><date>2011-01</date><risdate>2011</risdate><volume>79</volume><issue>1</issue><spage>304</spage><epage>314</epage><pages>304-314</pages><issn>0887-3585</issn><eissn>1097-0134</eissn><abstract>To investigate the effects of multiple protonation states on protein–ligand recognition, we generated alternative protonation states for selected titratable groups of ligands and receptors. The selection of states was based on the predicted pK
a of the unbound receptor and ligand and the proximity of titratable groups of the receptor to the binding site. Various ligand tautomer states were also considered. An independent docking calculation was run for each state. Several protocols were examined: using an ensemble of all generated states of ligand and receptor, using only the most probable state of the unbound ligand/receptor, and using only the state giving the most favorable docking score. The accuracies of these approaches were compared, using a set of 176 protein–ligand complexes (15 receptors) for which crystal structures and measured binding affinities are available. The best agreement with experiment was obtained when ligand poses from experimental crystal structures were used. For 9 of 15 receptors, using an ensemble of all generated protonation states of the ligand and receptor gave the best correlation between calculated and measured affinities. Proteins 2010. © 2010 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>21058298</pmid><doi>10.1002/prot.22883</doi><tpages>11</tpages></addata></record> |
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| subjects | binding pose Computer Simulation docking Hydrogen-Ion Concentration Ligands Models, Molecular Protein Binding Protein Structure, Tertiary protein-ligand binding affinity protonation state Receptors, Cytoplasmic and Nuclear - chemistry scoring function |
| title | Estimating binding affinities by docking/scoring methods using variable protonation states |
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