Article

Theoretical analysis of binding specificity of influenza viral hemagglutinin to avian and human receptors based on the fragment molecular orbital method.

Graduate School of Human Development and Environment, Kobe University, 3-11 Tsurukabuto, Nada, Kobe, Japan.
Computational Biology and Chemistry (impact factor: 1.55). 07/2008; 32(3):198-211. DOI:10.1016/j.compbiolchem.2008.03.006 pp.198-211
Source: PubMed

ABSTRACT The hemagglutinin (HA) protein of the influenza virus binds to the host cell receptor in the early stage of viral infection. A change in binding specificity from avian 2-3 to human 2-6 receptor is essential for optimal human-to-human transmission and pandemics. Therefore, it is important to reveal the key factors governing the binding affinity of HA-receptor complex at the molecular level for the understanding and prediction of influenza pandemics. In this work, on the basis of ab initio fragment molecular orbital (FMO) method, we have carried out the interaction energy analysis of HA-receptor complexes to quantitatively elucidate the binding specificity of HAs to avian and human receptors. To discuss the binding property of influenza HA comprehensively, a number of HAs from human H1, swine H1, avian H3 and avian H5 viruses were analyzed. We performed detailed investigations about the interaction patterns of complexes of various HAs and receptor analogues, and revealed that intra-molecular interactions between conserved residues in HA play an important role for HA-receptor binding. These results may provide a hint to understand the role of conserved acidic residues at the receptor binding site which are destabilized by the electrostatic repulsion with sialic acid. The calculated binding energies and interaction patterns between receptor and HAs are consistent with the binding specificities of each HA and thus explain the receptor binding mechanism. The calculated results in the present analysis have provided a number of viewpoints regarding the models for the HA-receptor binding specificity associated with mutated residues. Examples include the role of Glu190 and Gln226 for the binding specificity of H5 HA. Since H5 HA has not yet been adapted to human receptor and the mechanism of the specificity change is unknown, this result is helpful for the prediction of the change in receptor specificity associated with forthcoming possible pandemics.

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    Wei Hu
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    Journal of biomedical science and engineering 01/2010; 3:114-123.
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    Article: Rapid estimation of binding activity of influenza virus hemagglutinin to human and avian receptors.
    Yang Cao, Xiaoying Koh, Libo Dong, Xiangjun Du, Aiping Wu, Xilai Ding, Hongyu Deng, Yuelong Shu, Jianzhu Chen, Taijiao Jiang
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    ABSTRACT: A critical step for avian influenza viruses to infect human hosts and cause epidemics or pandemics is acquisition of the ability of the viral hemagglutinin (HA) to bind to human receptors. However, current global influenza surveillance does not monitor HA binding specificity due to a lack of rapid and reliable assays. Here we report a computational method that uses an effective scoring function to quantify HA-receptor binding activities with high accuracy and speed. Application of this method reveals receptor specificity changes and its temporal relationship with antigenicity changes during the evolution of human H3N2 viruses. The method predicts that two amino acid differences at 222 and 225 between HAs of A/Fujian/411/02 and A/Panama/2007/99 viruses account for their differences in binding to both avian and human receptors; this prediction was verified experimentally. The new computational method could provide an urgently needed tool for rapid and large-scale analysis of HA receptor specificities for global influenza surveillance.
    PLoS ONE 01/2011; 6(4):e18664. · 4.09 Impact Factor
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Keywords

ab initio fragment molecular orbital
 
avian H5 viruses
 
binding specificity
 
calculated results
 
conserved acidic residues
 
conserved residues
 
HA-receptor binding
 
HA-receptor binding specificity
 
HA-receptor complex
 
HA-receptor complexes
 
host cell receptor
 
human 2-6 receptor
 
human H1
 
influenza virus binds
 
intra-molecular interactions
 
mutated residues
 
receptor binding site
 
receptor specificity
 
specificity change
 
swine H1