title: Structurally conserved binding sites of hemagglutinin as targets for influenza drug and vaccine development.
abstract: ProBiS is a new method to identify the binding site of protein through local structural alignment against the nonredundant Protein Data Bank (PDB), which may result in unique findings compared to the energy-based, geometry-based, and sequence-based predictors. In this work, binding sites of Hemagglutinin (HA), which is an important target for drugs and vaccines in influenza treatment, have been revisited by ProBiS. For the first time, the identification of conserved binding sites by local structural alignment across all subtypes and strains of HA available in PDB is presented. ProBiS finds three distinctive conserved sites on HA's structure (named Site 1, Site 2, and Site 3). Compared to other predictors, ProBiS is the only one that accurately defines the receptor binding site (Site 1). Apart from that, Site 2, which is located slightly above the TBHQ binding site, is proposed as a potential novel conserved target for membrane fusion inhibitor. Lastly, Site 3, located around Helix A at the stem domain and recently targeted by cross-reactive antibodies, is predicted to be conserved in the latest H7N9 China 2013 strain as well. The further exploration of these three sites provides valuable insight in optimizing the influenza drug and vaccine development.
authors: Pharmaceutical Design and Simulation (PhDS) Laboratory, School of Pharmaceutical Sciences, Universiti Sains Malaysia , 11800 Minden, Pulau Pinang, Malaysia.
authors: Muhammad
authors: M
authors: Yusuf
authors: Janez
authors: J
authors: Konc
authors: Choi
authors: C
authors: Sy Bing
authors: Joanna
authors: J
authors: Trykowska Konc
authors: Nurul Bahiyah
authors: NB
authors: Ahmad Khairudin
authors: Dusanka
authors: D
authors: Janezic
authors: Habibah A
authors: HA
authors: Wahab
mesh_terms: D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000276:immunology; D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D019295:Computational Biology; D017124:Conserved Sequence; D055808:Drug Discovery; D018604:Epitope Mapping; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D008561:Membrane Fusion / Q000187:drug effects; D008958:Models, Molecular; D058990:Molecular Targeted Therapy; D011487:Protein Conformation; D014765:Viral Vaccines
chemical_list: D000914:Antibodies, Viral; D000998:Antiviral Agents; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D014765:Viral Vaccines