千葉工業大学 / 応用化学科 / 山本研究室
計算化学で生命・物質・環境・教育の問題解決
投稿:21-10-26

Mohini Yadav, CBI学会 (2021)

題名

Dynamic residue interaction network analysis of the neuraminidase H274Y mutant conferring drug resistance in influenza virus

学会

CBI学会 2021年大会, オンライン, 口頭発表, O1-2

発表者

Mohini Yadav / 山本 典史

概要

One of the major oseltamivir (OTV) resistant influenza virus strain exhibits His-to-Tyr mutation at residue 274 (H274Y) in N1 neuraminidase (NA). However, the molecular mechanism by which the H274Y mutation in N1 NA reduces its OTV binding affinity have not been fully elucidated. In this study, we theoretically investigated the dynamic correlation between the OTV binding site and H274Y mutation site of N1 NA using dynamic residue interaction network (dRIN) analysis based on molecular dynamics (MD) simulation. dRIN analysis revealed that the OTV binding site and H274Y mutation site of N1 NA interact via the three interface residues, S246, E276 and R292, connecting the two sites.  Due to H274Y mutation in N1 NA, the interaction between the residue 274 and three interface residues, S246, E276 and R292, significantly enhanced, resulting in significant decrease in the interaction between OTV and its surrounding 150-loop residues, D151 and R152. Hence, we concluded that such changes in residue interactions could reduce the OTV binding affinity of N1 NA, resulting in drug resistance influenza viruses.

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