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Prediction of avian influenza A binding preference to human receptor using conformational analysis of receptor bound to hemagglutinin
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Document Title
Prediction of avian influenza A binding preference to human receptor using conformational analysis of receptor bound to hemagglutinin
Author
Jongkon N., Mokmak W., Chuakheaw D., Shaw P.J., Tongsima S., Sangma C.
Name from Authors Collection
Affiliations
Cheminformatics Research Unit, Department of Chemistry, Faculty of Science, Kasetsart University, Thailand; National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, 113 Thailand Science Park, Phahonyothin Road, Klong 1, Klongluang, Pathumthani 12120, Thailand
Type
Article
Source Title
BMC Genomics
ISSN
14712164
Year
2009
Volume
10
Issue
SUPPL. 3
Open Access
Gold, Green
DOI
10.1186/1471-2164-10-S3-S24
Abstract
Background: It is known that the highly pathogenic avian influenza A virus H5N1 binds strongly and with high specificity to the avian-type receptor by its hemagglutinin surface protein. This specificity is normally a barrier to viral transmission from birds to humans. However, strains may emerge with mutated hemagglutinin, potentially changing the receptor binding preference from avian to human-type. This hypothesis has been proven correct, since viral isolates from Vietnam and Thailand have been found which have increased selectivity toward the human cell receptor. The change in binding preference is due to mutation, which can be computationally modelled. The aim of this study is to further explore whether computational simulation could be used as a prediction tool for host type selectivity in emerging variants. Results: Molecular dynamics simulation was employed to study the interactions between receptor models and hemagglutinin proteins from H5N1 strains A/Duck/Singapore/3/97, mutated A/Duck/Singapore/3/97 (Q222L, G224S, Q222L/G224S), A/Thailand/1(KAN-1)/2004, and mutated A/Thailand/1(KAN-1)/2004 (L129V/A134V). The avian receptor was represented by Siaα(2,3)Gal substructure and human receptor by Siaα(2,6)Gal. The glycoside binding conformation was monitored throughout the simulations since high selectivity toward a particular host occurs when the sialoside bound with the near-optimized conformation. Conclusion: The simulation results showed all hemagglutinin proteins used the same set of amino acid residues to bind with the glycoside; however, some mutations alter linkage preferences. Preference toward human-type receptors is associated with a positive torsion angle, while avian-type receptor preference is associated with a negative torsion angle. According to the conformation analysis of the bound receptors, we could predict the relative selectivity in accordance with in vitro experimental data when disaccharides receptor analogs were used. © 2009 Jongkon et al; licensee BioMed Central Ltd.
Industrial Classification
Knowledge Taxonomy Level 1
Knowledge Taxonomy Level 2
Knowledge Taxonomy Level 3
Funding Sponsor
Thailand Research Fund; Kasetsart University Research and Development Institute; Commission on Higher Education; National Center for Genetic Engineering and Biotechnology
License
CC BY
Rights
Author
Publication Source
Scopus