title: Docking of noncompetitive inhibitors into dengue virus type 2 protease: understanding the interactions with allosteric binding sites.
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 K(i) 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.
authors.affiliation: Pharmacy Department and Department of Molecular Medicine, Faculty of Medicine and Institute of Biological Sciences and Chemistry Department, Faculty of Science, Universiti Malaya, Kuala Lumpur, Malaysia.
authors.forename: Rozana
authors.initials: R
authors.lastname: Othman
authors.forename: Tan Siew
authors.initials: TS
authors.lastname: Kiat
authors.forename: Norzulaani
authors.initials: N
authors.lastname: Khalid
authors.forename: Rohana
authors.initials: R
authors.lastname: Yusof
authors.forename: E Irene
authors.initials: EI
authors.lastname: Newhouse
authors.forename: James S
authors.initials: JS
authors.lastname: Newhouse
authors.forename: Masqudul
authors.initials: M
authors.lastname: Alam
authors.forename: Noorsaadah Abdul
authors.initials: NA
authors.lastname: Rahman
mesh_terms: D000495:Allosteric Site; D003716:Dengue Virus / Q000187:drug effects* / Q000201:enzymology*; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D010447:Peptide Hydrolases / Q000737:chemistry* / Q000378:metabolism*; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D011480:Protease Inhibitors; D010447:Peptide Hydrolases