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
Hauptverfasser: Othman, Rozana, Kiat, Tan Siew, Khalid, Norzulaani, Yusof, Rohana, Irene Newhouse, E, Newhouse, James S, Alam, Masqudul, Rahman, Noorsaadah Abdul
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Sprache:eng
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Zusammenfassung: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.
ISSN:1549-9596
1520-5142
1549-960X
DOI:10.1021/ci700388k