title: Interaction and inhibition of dengue envelope glycoprotein with mammalian receptor DC-sign, an in-silico approach.
abstract: Membrane fusion is the central molecular event during the entry of enveloped viruses into cells. The critical agents of this process are viral surface proteins, primed to facilitate cell bilayer fusion. The important role of Dendritic-cell-specific ICAM3-grabbing non-integrin (DC-SIGN) in Dengue virus transmission makes it an attractive target to interfere with Dengue virus Propagation. Receptor mediated endocytosis allows the entry of virions due to the presence of endosomal membranes and low pH-induced fusion of the virus. DC-SIGN is the best characterized molecule among the candidate protein receptors and is able to mediate infection with the four serotypes of dengue virus (DENV). Unrestrained pair wise docking was used for the interaction of dengue envelope protein with DC-SIGN and monoclonal antibody 2G12. Pre-processed the PDB coordinates of dengue envelope glycoprotein and other candidate proteins were prepared and energy minimized through AMBER99 force field distributed in MOE software. Protein-protein interaction server, ZDOCK was used to find molecular interaction among the candidate proteins. Based on these interactions it was found that antibody successfully blocks the glycosylation site ASN 67 and other conserved residues present at DC-SIGN-Den-E complex interface. In order to know for certain, the exact location of the antibody in the envelope protein, co-crystallize of the envelope protein with these compounds is needed so that their exact docking locations can be identified with respect to our results.
authors.affiliation: Bioinformatics Research Laboratory, National Center of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore, Pakistan.
authors.forename: Masaud
authors.initials: M
authors.lastname: Shah
authors.forename: Abdul
authors.initials: A
authors.lastname: Wadood
authors.forename: Ziaur
authors.initials: Z
authors.lastname: Rahman
authors.forename: Tayyab
authors.initials: T
authors.lastname: Husnain
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D000080908:Broadly Neutralizing Antibodies; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000276:immunology; D019295:Computational Biology; D018360:Crystallography, X-Ray; D003715:Dengue / Q000517:prevention & control* / Q000635:transmission; D003716:Dengue Virus / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000235:genetics; D015483:HIV Antibodies; D006801:Humans; D037181:Lectins, C-Type / Q000737:chemistry* / Q000276:immunology; D016013:Likelihood Functions; D008957:Models, Genetic; D008958:Models, Molecular; D010802:Phylogeny; D011485:Protein Binding; D017510:Protein Folding; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000276:immunology; D016415:Sequence Alignment; D014759:Viral Envelope Proteins / Q000235:genetics*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D000911:Antibodies, Monoclonal; D000080908:Broadly Neutralizing Antibodies; D015815:Cell Adhesion Molecules; D018985:Epitopes, B-Lymphocyte; D015483:HIV Antibodies; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D014759:Viral Envelope Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C529157:2G12 monoclonal antibody