title: Targeting domain-III hinging of dengue envelope (DENV-2) protein by MD simulations, docking and free energy calculations.
abstract: The entry of the dengue virus is mediated by the conformational change in the envelope protein due to change in the endosomal pH. The structural study reveals that domain-III of the dengue envelope protein (DENV) shows the largest shift in its position during the entry of the virus. Therefore, targeting the hinge region of the domain-III may block the conformational changes in the DENV. In the present work, we have targeted the domain I/III hinge region using four known ligands used for the dengue envelope protein (serotype-2) and have intended to explore the specificity of one ligand R1 (5-(3-chlorophenyl)-N-(2-phenyl-2H-benzo[d][1,2,3]triazol-6-yl)furan-2-carboxamide) that succeeded the dengue inhibition by the molecular dynamics (MD) simulations in conjunction of the molecular docking and the binding free energy calculations. The residue interactions map shows Lys 296 of domain-III of the DENV-2, which might be responsible for binding small molecules between domain I/III interface, as an important residue conserved in all the dengue serotypes.
authors.affiliation: Biophysics Unit, Department of Physics, Deen Dayal Upadhyay Gorakhpur University, Gorakhpur, India. kshatresh@gmail.com.
authors.forename: Kshatresh Dutta
authors.identifier: http://orcid.org/0000-0001-8865-7602
authors.initials: KD
authors.lastname: Dubey
authors.affiliation: Biophysics Unit, Department of Physics, Deen Dayal Upadhyay Gorakhpur University, Gorakhpur, India.
authors.forename: Gargi
authors.initials: G
authors.lastname: Tiwari
authors.affiliation: Biophysics Unit, Department of Physics, Deen Dayal Upadhyay Gorakhpur University, Gorakhpur, India.
authors.forename: Rajendra Prasad
authors.initials: RP
authors.lastname: Ojha
mesh_terms: D019295:Computational Biology; D003716:Dengue Virus / Q000378:metabolism*; D005663:Furans / Q000378:metabolism*; D008024:Ligands; D062105:Molecular Docking Simulation; D054730:Protein Interaction Domains and Motifs; D013816:Thermodynamics; D014230:Triazoles / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D005663:Furans; D008024:Ligands; D014230:Triazoles; D014759:Viral Envelope Proteins
keywords: Binding affinity; Dengue virus; Envelope protein; MMPBSA; Residue interaction