ISSN 1000-6818CN 11-1892/O6CODEN WHXUEU
Acta Phys Chim Sin >> 2017,Vol.33>> Issue(3)>> 633-641     doi: 10.3866/PKU.WHXB201612052         中文摘要
Molecular Docking of Human-Like Receptor to Hemagglutinins of Avian Influenza A Viruses
DENG Ying-Chun, LIU Qing, HUANG Qiang
School of Life Sciences, Fudan University, Shanghai 200438, P. R. China
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Hemagglutinin (HA) is a glycoprotein located on the surface of the avian influenza A viruses. HA plays a key role in the infection process, binding to receptors on the host cell surface and mediating the fusion between viral and host endosomal membranes. In nature, influenza A virus undergoes continuous variation, particularly the amino acid sequence at the receptor binding site of HA. When the binding ability of HA variants towards human receptors becomes strong, influenza A virus can infect humans. To prevent the influenza A virus from infecting humans, proper assessments of the infectious risk posed are urgently needed. Screening of high risk virus strains by analyzing the binding ability of HA variants for human receptors through a high-throughput method would be particularly useful. In this study, we used H7 (a subtype of HA) as a subject and developed a molecular docking based theoretical calculation method to evaluate the affinity of HA variants for human receptors. The results showed that the binding affinity of H7 for human receptors is lower than that of H1, which shows a strong ability to infect humans. This result suggests that strains of the H7 subtype are generally weakly infectious in humans. Nevertheless, the calculation results also showed that some newly-found virus strains of the H7N9 subtype have a high binding affinity for human receptors, suggesting that the H7N9 subtype might include strains with a high risk for infecting humans. These results are consistent with the actual occurrence of the 2013 H7N9 epidemic. Our method may be used to rapidly predict the affinity of HA for human receptors and provides a theoretical basis for the risk assessment of the infectiousness of influenza A virus toward humans.

Keywords: Influenza A virus   Interspecies transmission   Receptor-specificity   Molecular docking   Binding free energy  
Received: 2016-10-28 Accepted: 2016-12-02 Publication Date (Web): 2016-12-05
Corresponding Authors: HUANG Qiang Email:

Fund: The project was supported by the National Natural Science Foundation of China (91430112,31671386) and Special Program for Applied Research on Super Computation of the NSFC-Guangdong Joint Fund (the Second Phase);China

Cite this article: DENG Ying-Chun, LIU Qing, HUANG Qiang. Molecular Docking of Human-Like Receptor to Hemagglutinins of Avian Influenza A Viruses[J]. Acta Phys. -Chim. Sin., 2017,33 (3): 633-641.    doi: 10.3866/PKU.WHXB201612052

(1) Taubenberger, J. K.; Morens, D. M. Rev. Sci. Tech. 2009, 28 (1), 187. doi: 10.20506/rst.28.1.1879
(2) dos Reis, M.; Hay, A. J.; Goldstein, R. A. J. Mol. Evol.2009, 69
(4), 333. doi: 10.1007/s00239-009-9282-x
(3) Neumann, G.; Noda, T.; Kawaoka, Y. Nature 2009, 459 (7249), 931. doi: 10.1038/nature08157
(4) Smith, G. J.; Vijaykrishna, D.; Bahl, J.; Lycett, S. J.; Worobey, M.; Pybus, O. G.; Ma, S. K.; Cheung, C. L.; Raghwani, J.; Bhatt, S.; Peiris, J. S. M.; Guan, Y.; Rambaut, A. Nature 2009, 459 (7250), 1122. doi: 10.1038/nature08182
(5) Nakajima, K.; Desselberger, U.; Palese, P. Nature 1978, 274, 334. doi: 10.1038/274334a0
(6) Johnson, N. P.; Mueller, J. Bull. Hist. Med. 2002, 76 (1), 105. doi: 10.1353/bhm.2002.0022
(7) Skehel, J. J.; Wiley, D. C. Annu. Rev. Biochem.2000, 69, 531. doi: 10.1146/annurev.biochem.69.1.531
(8) Matrosovich, M.; Stech, J.; Klenk, H. D. Rev. Sci. Tech. Off. Int.Epiz. 2009, 28 (1), 203. doi: 10.20506/rst.28.1.1870
(9) Matrosovich, M.; Tuzikov, A.; Bovin, N.; Gambaryan, A.; Klimov, A.; Castrucci, M. R.; Donatelli, I.; Kawaoka, Y. J. Virol.2000, 74 (18), 8502. doi: 10.1128/JVI.74.18.8502-8512.2000
(10) Tumpey, T. M.; Maines, T. R.; Van Hoeven, N.; Glaser, L.; Solorzano, A.; Pappas, C.; Cox, N. J.; Swayne, D. E.; Palese, P.; Katz, J. M.; Garcia-Sastre, A. Science 2007, 315, 655. doi: 10.1126/science.1136212
(11) Connor, R. J.; Kawaoka, Y.; Webster, R. G.; Paulson, J. C.; Virology 1994, 205, 17. doi: 10.1006/viro.1994.1615
(12) Stevens, J.; Blixt, O.; Tumpey, T. M.; Taubenberger, J. K.; Paulson, J. C.; Wilson, I. A. Science 2006, 312, 404. doi: 10.1126/science.1124513
(13) Xiong, X. L.; Martin, S. R.; Haire, L. F.; Wharton, S. A.; Daniels, R. S.; Bennett, M. S.; McCauley, J.W.; Collins, P. J.; Walker, P. A.; Skehel, J. J.; Gamblin, S. J. Nature 2013, 499, 496. doi: 10.1038/nature12372
(14) Wang, D.; Yang, L.; Gao, R.; Zhang, X.; Tan, Y.; Wu, A.; Zhu, W.; Zhou, J.; Zou, S.; Li, X. Y.; Sun, Y.; Zhang, Y.; Liu, Y.; Liu, T.; Xiong, Y.; Xu, J.; Chen, L.; Weng, Y.; Qi, X.; Guo, J.; Li, X.D.; Dong, J.; Huang, W.; Zhang, Y.; Dong, L.; Zhao, X.; Liu, L.; Lu, J.; Lan, Y.; Wei, H.; Xin, L.; Chen, Y.; Xu, C.; Chen, T.; Zhu, Y.; Jiang, T.; Feng, Z.; Yang, W.; Wang, Y.; Zhu, H.; Guan, Y.; Gao, G. F.; Li, D.; Han, J.; Wang, S.; Wu, G.; Shu, Y. Euro.Surveill.2014, 19 (25). doi: 10.2807/1560-7917.ES2014.19.25.20836
(15) Xu, R.; Mcbride, R.; Nycholat, C. M.; Paulson, J. C.; Wilson, I.A. J. Virol.2012, 86 (2), 982. doi: 10.1128/JVI.06322-11
(16) Zhang, W.; Shi, Y.; Qi, J.; Gao, F.; Li, Q.; Fan, Z.; Yan, J.; Gao, G. F. J. Virol.2013, 87 (10), 5949. doi: 10.1128/JVI.00545-13
(17) Liu, J.; Stevens, D. J.; Haire, L. F.; Walker, P. A.; Coombs, P. J.; Russell, R. J.; Gamblin, S. J.; Skehel, J. J. Proc. Natl. Acad. Sci.U. S. A. 2009, 106 (40), 17175. doi: 10.1073/pnas.0906849106
(18) Eisen, M. B.; Sabesan, S.; Skehel, J. J.; Wiley, D. C. Virology 1997, 232 (1), 19. doi: 10.1006/viro.1997.8526
(19) Liao, H. Y.; Hsu, C. H.; Wang, S. C.; Liang, C. H.; Yen, H. Y.; Su, C. Y.; Chen, C. H.; Jan, J. T.; Ren, C. T.; Chen, C. H.; Cheng, T. J.; Wu, C. Y.; Wong, C. H. J. Am. Chem. Soc.2010, 132 (42), 14849. doi: 10.1021/ja104657b
(20) Shi, Y.; Zhang, W.; Wang, F.; Qi, J.; Wu, Y.; Song, H.; Gao, F.; Bi, Y.; Zhang, Y.; Fan, Z.; Qin, C.; Sun, H.; Liu, J.; Haywood, J.; Liu, W.; Gong, W.; Wang, D.; Shu, Y.; Wang, Y.; Yan, J.; Gao, G. F. Science 2013, 342 (6155), 243. doi: 10.1126/science.1242917
(21) Deng, Y. L.; Yu, L.; Huang, Q. Acta Phys.-Chim. Sin. 2016, 32(9), 2355.[邓玉玲, 余璐, 黄强. 物理化学学报, 2016, 32(9), 2355.] doi: 10.3866/PKU.WHXB201605171
(22) Goodsell, D. S.; Olson, A. J. Proteins:Struct. Funct. Genet.1990, 8 (3), 195. doi: 10.1002/prot.340080302
(23) Huey, R.; Morris, G. M.; Olson, A. J.; Goodsell, D. S. J.Comput. Chem.2007, 28 (6), 1145. doi: 10.1002/jcc.20634
(24) Morris, G. M.; Huey, R.; Lindstrom, W.; Sanner, M. F.; Belew, R. K.; Goodsell, D. S.; Olson, A. J. J. Comput. Chem.2009, 30(16), 2785. doi: 10.1002/jcc.21256
(25) Forli, S.; Olson, A. J. J. Med. Chem.2012, 55 (2), 623. doi: 10.1021/jm2005145
(26) Gamblin, S. J.; Haire, L. F.; Russell, R. J.; Stevens, D. J.; Xiao, B.; Ha, Y.; Vasisht, N.; Steinhauer, D. A.; Daniels, R. S.; Elliot, A.; Wiley, D. C.; Skehel, J. J. Science 2004, 303 (5665), 1838. doi: 10.1126/science.1093155
(27) Xu, R.; Ekiert, D. C.; Krause, J. C.; Hai, R.; Crowe, J. E., Jr.; Wilson, I. A. Science 2010, 328 (5976), 357. doi: 10.1126/science.1186430
(28) Yang, H.; Carney, P.; Stevens, J. PLoS Curr.2010, 2, RRN1152. doi: 10.1371/currents.RRN1152
(29) Fraser, C.; Donnelly, C. A.; Cauchemez, S.; Hanage, W. P.; VanKerkhove, M. D.; Hollingsworth, T. D.; Griffin, J.; Baggaley, R.F.; Jenkins, H. E.; Lyons, E. J.; Jombart, T.; Hinsley, W. R.; Grassly, N. C.; Balloux, F.; Ghani, A. C.; Ferguson, N. M.; Rambaut, A.; Pybus, O. G.; Lopez-Gatell, H.; Alpuche-Aranda, C. M.; Chapela, I. B.; Zavala, E. P.; Guevara, D. M.; Checchi, F.; Garcia, E.; Hugonnet, S.; Roth, C. Science 2009, 324 (5934), 1557. doi: 10.1126/science.1176062
(30) Munayco, C. V.; Gomez, J.; Laguna-Torres, V. A.; Arrasco, J.; Kochel, T. J.; Fiestas, V.; Garcia, J.; Perez, J.; Torres, I.; Condori, F.; Nishiura, H.; Chowell, G. Euro. Surveill. 2009, 14 (32), 6.
(31) Lam, T. T.; Zhou, B.; Wang, J.; Chai, Y.; Shen, Y.; Chen, X.; Ma, C.; Hong, W.; Chen, Y.; Zhang, Y.; Duan, L.; Chen, P.; Jiang, J.; Zhang, Y.; Li, L.; Poon, L. L.; Webby, R. J.; Smith, D.K.; Leung, G. M.; Peiris, J. S.; Holmes, E. C.; Guan, Y.; Zhu, H.Nature 2015, 522 (7554), 102. doi: 10.1038/nature14348
(33) Tharakaraman, K.; Jayaraman, A.; Raman, R.; Viswanathan, K.; Stebbins, N.W.; Johnson, D.; Shriver, Z.; Sasisekharan, V.; Sasisekharan, R. Cell 2013, 153 (7), 1486. doi: 10.1016/j.cell.2013.05.034
(34) Ding, H.; Chen, Y.; Yu, Z.; Horby, P. W;Wang, F.; Hu, J.; Yang, X.; Mao, H.; Qin, S.; Chai, C.; Liu, S.; Chen, E.; Yu, H. BMC Infect. Dis.2014, 14, 698. doi: 10.1186/s12879-014-0698-6

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