Antigen-antibody interactions of influenza virus hemagglutinin revealed by the fragment molecular orbital calculation

Effective interactions between amino acid residues in antigen-antibody complex of influenza virus hemagglutinin (HA) protein can be evaluated in terms of the inter-fragment interaction energy (IFIE) analysis with the fragment molecular orbital (FMO) method, in which each fragment contains the side chain of corresponding amino acid residue. We have carried out the FMO-MP2 (second-order Moeller-Plesset) calculation for the complex of HA antigen and Fab antibody of influenza virus H3N2 A/Aichi/2/68 and obtained the IFIE values between each amino acid residue in HA and the whole antibody as the sums over the residues contained in the latter. Combining this IFIE data with experimental data for hemadsorption activity of HA mutants, we succeeded in theoretically explaining the mutations in HA observed after the emergence of influenza virus H3N2 A/Aichi/2/68 in an earlier study, except for those of THR83. In the present study, we employ an alternative way of fragment division in the FMO calculation at the carbonyl C site of the peptide bond instead of the C_α site used in the previous work, which provides revised IFIE values consistent with all the historical mutation data in the antigenic region E of HA including the case of THR83 in the present prediction scheme for probable mutations in HA.