title: Theoretical investigation on the binding specificity of sialyldisaccharides with hemagglutinins of influenza A virus by molecular dynamics simulations.
abstract: Recognition of cell-surface sialyldisaccharides by influenza A hemagglutinin (HA) triggers the infection process of influenza. The changes in glycosidic torsional linkage and the receptor conformations may alter the binding specificity of HAs to the sialylglycans. In this study, 10-ns molecular dynamics simulations were carried out to examine the structural and dynamic behavior of the HAs bound with sialyldisaccharides Neu5Acα(2-3)Gal (N23G) and Neu5Acα(2-6)Gal (N26G). The analysis of the glycosidic torsional angles and the pair interaction energy between the receptor and the interacting residues of the binding site reveal that N23G has two binding modes for H1 and H5 and a single binding mode for H3 and H9. For N26G, H1 and H3 has two binding modes, and H5 and H9 has a single binding mode. The direct and water-mediated hydrogen bonding interactions between the receptors and HAs play dominant roles in the structural stabilization of the complexes. It is concluded from pair interaction energy and Molecular Mechanic-Poisson-Boltzmann Surface Area calculations that N26G is a better receptor for H1 when compared with N23G. N23G is a better receptor for H5 when compared with N26G. However, H3 and H9 can recognize N23G and N26G in equal binding specificity due to the marginal energy difference (≈2.5 kcal/mol). The order of binding specificity of N23G is H3 > H5 > H9 > H1 and N26G is H1 > H3 > H5 > H9, respectively. The proposed conformational models will be helpful in designing inhibitors for influenza virus.
authors: Department of Physics, Manonmaniam Sundaranar University, Tirunelveli, Tamilnadu 627 012, India.
authors: Thanu R K
authors: TR
authors: Priyadarzini
authors: Jeyasigamani F A
authors: JF
authors: Selvin
authors: M Michael
authors: MM
authors: Gromiha
authors: Kazuhiko
authors: K
authors: Fukui
authors: Kasinadar
authors: K
authors: Veluraja
mesh_terms: D004187:Disaccharides / Q000737:chemistry* / Q000378:metabolism; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000378:metabolism; D009980:Influenza A virus / Q000737:chemistry* / Q000378:metabolism; D056004:Molecular Dynamics Simulation
chemical_list: D004187:Disaccharides; D019267:Hemagglutinin Glycoproteins, Influenza Virus