Computational analysis of a conformational epitope of a broadly neutralizing antibody in influenza A virus hemagglutinin

2016 Fiscal Year Final Research Report

• Project/Area Number: 25450417
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Veterinary medical science
• Research Institution: Hokkaido University
• Principal Investigator: Igarashi Manabu 北海道大学, 人獣共通感染症リサーチセンター, 准教授 (10374240)
• Co-Investigator(Renkei-kenkyūsha): TAKADA AYATO 北海道大学, 人獣共通感染症リサーチセンター, 教授 (10292062)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: インフルエンザ / ウイルス / 抗体 / 計算科学 / 分子動力学 / 分子モデリング

Outline of Final Research Achievements

The HA of influenza A viruses is classified into 16 subtypes (H1-H16). We have previously reported a cross-reactive antibody, designated S139/1, which neutralizes H1, H2, H3, H13, and H16 subtypes. In this study, we characterized the S139/1 recognition sites on different HAs by computational methods such as molecular modeling and dynamics simulations. We investigated the contribution of individual residues on each HA to the interaction with S139/1, and found that amino acids at 10 positions on HA strongly contributed to S139/1 binding as for the strains neutralized by S139/1. Analysis of hydrogen bond interactions emphasized that the residues at positions 156, 158 and 193 were the most important for S139/1 binding. Indeed, amino acid substitutions at these three positions were experimentally observed in the mutant viruses escaping from neutralization by S139/1. Thus, our computational methods identified the amino acid residues critical for the cross-neutralizing activity of S139/1.

Free Research Field

計算構造生物学