Docking of noncompetitive inhibitors into dengue virus type 2 protease: understanding the interactions with allosteric binding sites

Othman, R. and Kiat, T.S. and Khalid, N. and Yusof, R. and Newhouse, E.I. and Newhouse, J.S. and Alam, M. and Rahman, N.A. (2008) Docking of noncompetitive inhibitors into dengue virus type 2 protease: understanding the interactions with allosteric binding sites. Journal of Chemical Information and Modeling, 48 (8). pp. 1582-1591. ISSN 1549-9596

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Abstract

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 K4 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.

Item Type: Article
Uncontrolled Keywords: Active sites Automated docking Backbone carbonyl Catalytic triad Chalcones Dengue virus Experimental data H-bonding interactions Inhibitory activities Structural informations Structure-activity relationship Arsenic compounds Binding energy Biochemistry Chemotherapy Chlorine compounds Docking Drug delivery Drug dosage Flow interactions Ligands Viruses Binding sites ligand peptide hydrolase proteinase inhibitor article binding site chemical structure chemistry drug effect enzymology metabolism structure activity relation Allosteric Site Models, Molecular Molecular Structure Peptide Hydrolases Protease Inhibitors
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Science > Institute of Biological Sciences
Depositing User: miss munirah saadom
Date Deposited: 24 Apr 2013 03:23
Last Modified: 24 Apr 2013 03:23
URI: http://eprints.um.edu.my/id/eprint/5928

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