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Computational Analysis of the Interaction Energies between Amino Acid Residues of the Measles Virus Hemagglutinin and Its Receptors.

Authors
  • Xu, Fengqi1
  • Tanaka, Shigenori2
  • Watanabe, Hirofumi3
  • Shimane, Yasuhiro4
  • Iwasawa, Misako5
  • Ohishi, Kazue6
  • Maruyama, Tadashi7
  • 1 Department of Computational Science, Graduate School of System Informatics, Kobe University, 1-1, Rokkodai, Nada-ku, Kobe, Hyogo 657-8501, Japan. [email protected]. , (Japan)
  • 2 Department of Computational Science, Graduate School of System Informatics, Kobe University, 1-1, Rokkodai, Nada-ku, Kobe, Hyogo 657-8501, Japan. [email protected]. , (Japan)
  • 3 Education Center on Computational Science and Engineering, Kobe University, 7-1-48, Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. [email protected]. , (Japan)
  • 4 Center for Marine Biosciences, Japan Agency for Marine-Earth Science and Technology, 2-15, Natsushima, Yokosuka, Kanagawa 237-0061, Japan. [email protected]. , (Japan)
  • 5 Center for Earth Information Science and Technology, Japan Agency for Marine-Earth Science and Technology, 3173-25, Showa-machi, Kanazawa-ku, Yokohama, Kanagawa 236-0001, Japan. [email protected]. , (Japan)
  • 6 Faculty of Engineering, Tokyo Polytechnic University, 1583, Iiyama, Atsugi, Kanagawa 243-0297, Japan. [email protected]. , (Japan)
  • 7 Center for Marine Biosciences, Japan Agency for Marine-Earth Science and Technology, 2-15, Natsushima, Yokosuka, Kanagawa 237-0061, Japan. [email protected]. , (Japan)
Type
Published Article
Journal
Viruses
Publisher
MDPI AG
Publication Date
May 03, 2018
Volume
10
Issue
5
Identifiers
DOI: 10.3390/v10050236
PMID: 29751531
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Measles virus (MV) causes an acute and highly devastating contagious disease in humans. Employing the crystal structures of three human receptors, signaling lymphocyte-activation molecule (SLAM), CD46, and Nectin-4, in complex with the measles virus hemagglutinin (MVH), we elucidated computationally the details of binding energies between the amino acid residues of MVH and those of the receptors with an ab initio fragment molecular orbital (FMO) method. The calculated inter-fragment interaction energies (IFIEs) revealed a number of significantly interacting amino acid residues of MVH that played essential roles in binding to the receptors. As predicted from previously reported experiments, some important amino-acid residues of MVH were shown to be common but others were specific to interactions with the three receptors. Particularly, some of the (non-polar) hydrophobic residues of MVH were found to be attractively interacting with multiple receptors, thus indicating the importance of the hydrophobic pocket for intermolecular interactions (especially in the case of Nectin-4). In contrast, the electrostatic interactions tended to be used for specific molecular recognition. Furthermore, we carried out FMO calculations for in silico experiments of amino acid mutations, finding reasonable agreements with virological experiments concerning the substitution effect of residues. Thus, the present study demonstrates that the electron-correlated FMO method is a powerful tool to search exhaustively for amino acid residues that contribute to interactions with receptor molecules. It is also applicable for designing inhibitors of MVH and engineered MVs for cancer therapy.

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