Prediction of probable mutations in influenza virus hemagglutinin protein based on large-scale ab initio fragment molecular orbital calculations

Akio Yoshioka, Kaori Fukuzawa, Yuji Mochizuki, Katsumi Yamashita, Tatsuya Nakano, Yoshio Okiyama, Eri Nobusawa, Katsuhisa Nakajima, Shigenori Tanaka

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

Ab initio electronic-state calculations for influenza virus hemagglutinin (HA) trimer complexed with Fab antibody were performed on the basis of the fragment molecular orbital (FMO) method at the second and third-order Møller-Plesset (MP2 and MP3) perturbation levels. For the protein complex containing 2351 residues and 36,160 atoms, the inter-fragment interaction energies (IFIEs) were evaluated to illustrate the effective interactions between all the pairs of amino acid residues. By analyzing the calculated data on the IFIEs, we first discussed the interactions and their fluctuations between multiple domains contained in the trimer complex. Next, by combining the IFIE data between the Fab antibody and each residue in the HA antigen with experimental data on the hemadsorption activity of HA mutants, we proposed a protocol to predict probable mutations in HA. The proposed protocol based on the FMO-MP2.5 calculation can explain the historical facts concerning the actual mutations after the emergence of A/Hong Kong/1/68 influenza virus with subtype H3N2, and thus provides a useful methodology to enumerate those residue sites likely to mutate in the future.

Original languageEnglish
Pages (from-to)110-119
Number of pages10
JournalJournal of Molecular Graphics and Modelling
Volume30
DOIs
Publication statusPublished - 2011 Sep
Externally publishedYes

Keywords

  • Antibody
  • Fragment molecular orbital (FMO) method
  • Hemagglutinin (HA)
  • Influenza
  • Mutation

ASJC Scopus subject areas

  • Spectroscopy
  • Physical and Theoretical Chemistry
  • Computer Graphics and Computer-Aided Design
  • Materials Chemistry

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