title: Interaction energy analysis on specific binding of influenza virus hemagglutinin to avian and human sialosaccharide receptors: importance of mutation-induced structural change.
abstract: On the basis of available molecular structures registered in Protein Data Bank, we have theoretically carried out the interaction energy analysis for the complexes of influenza virus hemagglutinin (HA) proteins and sialosaccharide receptor analogs of host cells. Employing the fragment molecular orbital method for quantum-chemical calculations, the differences in magnitude and pattern of the interactions between the amino acid residues of avian-type (H7N3) or human-type (H7N9) HA and each saccharide part of avian or human receptor were studied in order to elucidate the molecular mechanism of avian-to-human infectious transmission of influenza virus. We have thus confirmed quantitatively that the mutations from the avian HA to the human HA significantly strengthened the binding affinity of human HA to human receptor, while retaining the affinity to avian receptor. In addition to direct effects regarding the changes of interactions between the altered residues and the receptors, we have also found the importance of indirect effects in which structural changes caused by the mutations play vital roles to modify the intermolecular interactions.
authors: Graduate School of System Informatics, Kobe University, 1-1, Rokkodai, Nada-ku, Kobe 657-8501, Japan.
authors: Satoshi
authors: S
authors: Anzaki
authors: Institute of Industrial Science, The University of Tokyo, 4-6-1, Komaba, Meguro-ku, Tokyo 153-8505, Japan.
authors: Chiduru
authors: C
authors: Watanabe
authors: Institute of Industrial Science, The University of Tokyo, 4-6-1, Komaba, Meguro-ku, Tokyo 153-8505, Japan; Mizuho Information and Research Institute Inc., 2-3, Kanda Nishi-cho, Chiyoda-ku, Tokyo 101-8443, Japan.
authors: Kaori
authors: K
authors: Fukuzawa
authors: Institute of Industrial Science, The University of Tokyo, 4-6-1, Komaba, Meguro-ku, Tokyo 153-8505, Japan; Department of Chemistry and Research Center for Smart Molecules, Faculty of Science, Rikkyo University, 3-34-1, Nishi-Ikebukuro, Toshima-ku, Tokyo 171-8501, Japan.
authors: Yuji
authors: Y
authors: Mochizuki
authors: Graduate School of System Informatics, Kobe University, 1-1, Rokkodai, Nada-ku, Kobe 657-8501, Japan. Electronic address: tanaka2@kobe-u.ac.jp.
authors: Shigenori
authors: S
authors: Tanaka
mesh_terms: D000595:Amino Acid Sequence; D030161:Avian Proteins / Q000737:chemistry*; D001665:Binding Sites; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D057920:Influenza A Virus, H7N3 Subtype / Q000737:chemistry; D064766:Influenza A Virus, H7N9 Subtype / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D030161:Avian Proteins; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011991:Receptors, Virus
keywords: Fragment molecular orbital (FMO) method; Hemagglutinin (HA); Influenza; Mutation; Receptor binding