Recognition of hemagglutinin in avian influenza virus to human sialic-galactose using in silico technique

Abstract

Influenza virus hemagglutinin is an essential protein for the binding to host cell receptor. Rare cases of human infection with avian influenza virus subtype H5N1 is thought to be associated with poor binding of avian viral H5 to human sialic acid-α2,6-galactose receptor (SAα2,6Gal). It was found that mutations at positions 129 and 222 enhanced specificity of H5N1 viruses to recognize SAα2,6Gal. Comparisons between residues within 5 Å from the binding pocket of the H3 and those of the H5 have revealed substantial differences in terms of amino acids and structures. In this study, molecular modeling and molecular dynamics simulation techniques have been employed to investigate the binding and recognition roles of these amino acids to SAα2,6Gal . Molecular dynamics simulations have been carried out for a number of single mutants including S129N, N182S, E186D, Q222V and G224S. Binding energy of the complexes between the SAα2,6Gal receptor and all the H5 proteins were computed and compared. The results show that S129N and Q222V exhibit a greater binding free energy to the SAα2,6Gal receptor compared to the wild-type. This finding would be useful for prediction of the critical amino acid residues which are possibly associated with the efficient transmission of H5N1 subtype from avian to human.