computational studies on the substrate interactions of influenza a virus pb2 subunit底物相互作用的计算研究甲型流感病毒pb2亚基.pdf

Computational Studies on the Substrate Interactions of Influenza A Virus PB2 Subunit 1 1,2 1 2,4 1 1 2,4 2,3 Ya-Jun Wang , Jing-Fang Wang *, Jie Ping , Yao Yu , Ying Wang , Peng Lian , Xuan Li , Yi-Xue Li , Pei Hao2,5* 1 Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China, 2 Shanghai Center for Bioinformation and Technology, Shanghai, China, 3 Bioinformatics Center, Key Laboratory of Systems Biology, Chinese Academy of Sciences, Shanghai, China, 4 Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China, 5 Institute of Pasteur, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China Abstract Influenza virus, which spreads around the world in seasonal epidemics and leads to large numbers of deaths every year, has several ribonucleoproteins in the central core of the viral particle. These viral ribonucleoproteins can specifically bind the conserved 39 and 59 caps of the viral RNAs with responsibility for replication and transcription of the viral RNA in the nucleus of infected cells. A fundamental question of most importance is that how the cap-binding proteins in the influenza virus discriminates between capped RNAs and non-capped ones. To get an answer, we performed molecular dynamics simulations and free energy calculations on the influenza A virus PB2 subunit, an important component of the RNP complexes, with a cap analog m7GTP. Our calculations showed that some key residues in the active site, such as Arg355, His357, Glu361 as well as Gln406, could offer significant hydrogen bonding and hydrophobic interactions with t