Docking of Noncompetitive Inhibitors into Dengue Virus Type 2 Protease: Understanding the Interactions with Allosteric Binding Sites
A group of flavanones and their chalcones, isolated from Boesenbergia rotunda L., were previously reported to show varying degrees of noncompetitive inhibitory activities toward Dengue virus type 2 (Den2) protease. Results obtained from automated docking studies are in agreement with experimental da...
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| Veröffentlicht in: | Journal of Chemical Information and Modeling 2008-08, Vol.48 (8), p.1582-1591 |
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| container_title | Journal of Chemical Information and Modeling |
| container_volume | 48 |
| creator | Othman, Rozana Kiat, Tan Siew Khalid, Norzulaani Yusof, Rohana Irene Newhouse, E Newhouse, James S Alam, Masqudul Rahman, Noorsaadah Abdul |
| description | A group of flavanones and their chalcones, isolated from Boesenbergia rotunda L., were previously reported to show varying degrees of noncompetitive inhibitory activities toward Dengue virus type 2 (Den2) protease. Results obtained from automated docking studies are in agreement with experimental data in which the ligands were shown to bind to sites other than the active site of the protease. The calculated Ki values are very small, indicating that the ligands bind quite well to the allosteric binding site. Greater inhibition by pinostrobin, compared to the other compounds, can be explained by H-bonding interaction with the backbone carbonyl of Lys74, which is bonded to Asp75 (one of the catalytic triad residues). In addition, structure−activity relationship analysis yields structural information that may be useful for designing more effective therapeutic drugs against dengue virus infections. |
| doi_str_mv | 10.1021/ci700388k |
| format | Article |
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In addition, structure−activity relationship analysis yields structural information that may be useful for designing more effective therapeutic drugs against dengue virus infections.</description><identifier>ISSN: 1549-9596</identifier><identifier>EISSN: 1520-5142</identifier><identifier>EISSN: 1549-960X</identifier><identifier>DOI: 10.1021/ci700388k</identifier><identifier>PMID: 18656912</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Allosteric Site ; Binding sites ; Chemical compounds ; Computational Chemistry ; Dengue Virus - drug effects ; Dengue Virus - enzymology ; Ligands ; Models, Molecular ; Molecular Structure ; Molecules ; Peptide Hydrolases - chemistry ; Peptide Hydrolases - metabolism ; Protease Inhibitors - chemistry ; Protease Inhibitors - pharmacology ; Proteases ; Structure-Activity Relationship ; Studies ; Viruses</subject><ispartof>Journal of Chemical Information and Modeling, 2008-08, Vol.48 (8), p.1582-1591</ispartof><rights>Copyright © 2008 American Chemical Society</rights><rights>Copyright American Chemical Society Aug 2008</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a378t-d765c3145e8e0a0764bdae056ab6066270a81b8128ac9385fcbc509d8f19d5ce3</citedby><cites>FETCH-LOGICAL-a378t-d765c3145e8e0a0764bdae056ab6066270a81b8128ac9385fcbc509d8f19d5ce3</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/ci700388k$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/ci700388k$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18656912$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Othman, Rozana</creatorcontrib><creatorcontrib>Kiat, Tan Siew</creatorcontrib><creatorcontrib>Khalid, Norzulaani</creatorcontrib><creatorcontrib>Yusof, Rohana</creatorcontrib><creatorcontrib>Irene Newhouse, E</creatorcontrib><creatorcontrib>Newhouse, James S</creatorcontrib><creatorcontrib>Alam, Masqudul</creatorcontrib><creatorcontrib>Rahman, Noorsaadah Abdul</creatorcontrib><title>Docking of Noncompetitive Inhibitors into Dengue Virus Type 2 Protease: Understanding the Interactions with Allosteric Binding Sites</title><title>Journal of Chemical Information and Modeling</title><addtitle>J. Chem. Inf. Model</addtitle><description>A group of flavanones and their chalcones, isolated from Boesenbergia rotunda L., were previously reported to show varying degrees of noncompetitive inhibitory activities toward Dengue virus type 2 (Den2) protease. Results obtained from automated docking studies are in agreement with experimental data in which the ligands were shown to bind to sites other than the active site of the protease. The calculated Ki values are very small, indicating that the ligands bind quite well to the allosteric binding site. Greater inhibition by pinostrobin, compared to the other compounds, can be explained by H-bonding interaction with the backbone carbonyl of Lys74, which is bonded to Asp75 (one of the catalytic triad residues). In addition, structure−activity relationship analysis yields structural information that may be useful for designing more effective therapeutic drugs against dengue virus infections.</description><subject>Allosteric Site</subject><subject>Binding sites</subject><subject>Chemical compounds</subject><subject>Computational Chemistry</subject><subject>Dengue Virus - drug effects</subject><subject>Dengue Virus - enzymology</subject><subject>Ligands</subject><subject>Models, Molecular</subject><subject>Molecular Structure</subject><subject>Molecules</subject><subject>Peptide Hydrolases - chemistry</subject><subject>Peptide Hydrolases - metabolism</subject><subject>Protease Inhibitors - chemistry</subject><subject>Protease Inhibitors - pharmacology</subject><subject>Proteases</subject><subject>Structure-Activity Relationship</subject><subject>Studies</subject><subject>Viruses</subject><issn>1549-9596</issn><issn>1520-5142</issn><issn>1549-960X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpl0V1v0zAUBuAIgdgHXPAHkIU0pF0EbCf-yO5Gx9ZJBSqtQ9xZjnOyek3tznbGds8PJ1WqTYIrW_bj9xz5ZNk7gj8RTMlnYwXGhZSrF9k-YRTnjJT05XZfVnnFKr6XHcR4O5ii4vR1tkckZ7widD_7c-bNyrob5Fv03Tvj1xtINtl7QJduaWubfIjIuuTRGbibHtBPG_qIFo8bQBTNg0-gI5yga9dAiEm7ZpuWltv3CYI2yXoX0W-blui063wcDq1BX-wIr2yC-CZ71eouwtvdephdn39dTKb57MfF5eR0lutCyJQ3gjNTkJKBBKyx4GXdaMCM65pjzqnAWpJaEiq1qQrJWlMbhqtGtqRqmIHiMPs45m6Cv-shJrW20UDXaQe-j4pXJReiLAf44R946_vght4UJZyWvJRiQMcjMsHHGKBVm2DXOjwqgtV2LuppLoN9vwvs6zU0z3I3iAHkI7DDBz083euwUlwUgqnF_ErNJr8uvk3Pp2o--KPRaxOfm_u_8F8V4aTD</recordid><startdate>20080801</startdate><enddate>20080801</enddate><creator>Othman, Rozana</creator><creator>Kiat, Tan Siew</creator><creator>Khalid, Norzulaani</creator><creator>Yusof, Rohana</creator><creator>Irene Newhouse, E</creator><creator>Newhouse, James S</creator><creator>Alam, Masqudul</creator><creator>Rahman, Noorsaadah Abdul</creator><general>American Chemical Society</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>7SC</scope><scope>7SR</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>JQ2</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>7X8</scope></search><sort><creationdate>20080801</creationdate><title>Docking of Noncompetitive Inhibitors into Dengue Virus Type 2 Protease: Understanding the Interactions with Allosteric Binding Sites</title><author>Othman, Rozana ; 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| source | MEDLINE; American Chemical Society Journals |
| subjects | Allosteric Site Binding sites Chemical compounds Computational Chemistry Dengue Virus - drug effects Dengue Virus - enzymology Ligands Models, Molecular Molecular Structure Molecules Peptide Hydrolases - chemistry Peptide Hydrolases - metabolism Protease Inhibitors - chemistry Protease Inhibitors - pharmacology Proteases Structure-Activity Relationship Studies Viruses |
| title | Docking of Noncompetitive Inhibitors into Dengue Virus Type 2 Protease: Understanding the Interactions with Allosteric Binding Sites |
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