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Acta Physico-Chimica Sinca  2017, Vol. 33 Issue (3): 633-641    DOI: 10.3866/PKU.WHXB201612052
ARTICLE     
Molecular Docking of Human-Like Receptor to Hemagglutinins of Avian Influenza A Viruses
Ying-Chun DENG,Qing LIU,Qiang HUANG*()
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Abstract  

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.



Key wordsInfluenza A virus      Interspecies transmission      Receptor-specificity      Molecular docking      Binding free energy     
Received: 28 October 2016      Published: 05 December 2016
MSC2000:  O641  
Fund:  the National Natural Science Foundation of China(91430112);the National Natural Science Foundation of China(31671386);Special Program for Applied Research on Super Computation of the NSFC-Guangdong Joint Fund (the Second Phase), China
Corresponding Authors: Qiang HUANG     E-mail: huangqiang@fudan.edu.cn
Cite this article:

Ying-Chun DENG,Qing LIU,Qiang HUANG. Molecular Docking of Human-Like Receptor to Hemagglutinins of Avian Influenza A Viruses. Acta Physico-Chimica Sinca, 2017, 33(3): 633-641.

URL:

http://www.whxb.pku.edu.cn/10.3866/PKU.WHXB201612052     OR     http://www.whxb.pku.edu.cn/Y2017/V33/I3/633

Fig 1 Structures of HA and LSTc (a) HA (PDB code: 4JTV); (b) human-like receptor analogue (LSTc)
Fig 2 Molecular docking flowchart of HA variants
Strain The lowest binding free energy Strain The lowest binding free energy
(kJ·mol-1) (kJ·mol-1)
A/Guangdong/05/2013(H7N9) -53.3 A/Shanghai/4/2013(H7N9) -47.1
A/Hong Kong/734/2014(H7N9) -52.0 A/Hangzhou/10-1/2014(H7N9) -47.0
A/Shanghai/05/2013(H7N9) -50.2 A/Taiwan/1/2014(H7N9) -46.9
A/Huzhou/5/2013(H7N9) -50.1 A/Nanjing/M2/2013(H7N9) -46.9
A/Hong Kong/5581/2014(H7N9) -50.0 A/Jiangsu/05/2013(H7N9) -46.9
A/Shandong/01/2013 (H7N9) -49.4 A/Shanghai/1/2013(H7N9) -46.2
A/Hong Kong/5731/2014(H7N9) -49.3 A/Shanghai/3/2013(H7N9) -46.1
A/Anhui/1/2013(H7N9) -49.1 A/Zhejiang/1/2013(H7N9) -46.0
A/Zhejiang/02/2013(H7N9) -48.9 A/Jiangsu/03/2013(H7N9) -46.0
A/Shanghai/07/2013(H7N9) -48.8 A/Nanjing/3/2013(H7N9) -45.8
A/Zhejiang/20/2013(H7N9) -48.8 A/Taiwan/2/2013(H7N9) -45.7
A/Hangzhou/17-1 /2014(H7N9) -48.7 A/Fujian/01/2013 (H7N9) -45.6
A/Huzhou/6/2013(H7N9) -48.4 A/Anhui/02/2013(H7N9) -45.4
A/Anhui/03/2013(H7N9) -47.9 A/Hong Kong/4495/2014(H7N9) -45.0
A/Hong Kong/5942/2013(H7N9) -47.9 A/Jiangsu/01/2013(H7N9) -44.8
A/Hangzhou/3/2013(H7N9) -47.5 A/Guangzhou/1/2014(H7N9) -44.5
A/Zhejiang/22/2013(H7N9) -47.5 A/Hong Kong/8122430/2014(H7N9) -44.3
A/Jiangsu/04/2013(H7N9) -47.4 A/Jiangsu/09/2013(H7N9) -44.0
A/Huzhou/4/2013(H7N9) -47.4 A/Nanjing/5/2013(H7N9) -43.8
A/Shanghai/9/2013(H7N9) -47.2 A/Turkey/Italy/214845/2002(H7N3) -46.7
Table 1 Lowest binding free energy of HA and LSTc
Strain The lowest binding free energy/(kJ·mol-1) Strain The lowest binding free energy/(kJ·mol-1)
A/Shanghai/1/2013(H7N9) -46.2 A/Anhui/03/2013(H7N9) -47.9
A/Shanghai/3/2013(H7N9) -46.1 A/Jiangsu/01/2013(H7N9) -44.8
A/Shanghai/4/2013(H7N9) -47.1 A/Zhejiang/02/2013(H7N9) -48.9
A/Anhui/1/2013(H7N9) -49.1 A/Jiangsu/09/2013(H7N9) -44.0
Table 2 The lowest binding free energy of HA from 8 fatal H7N9 isolates
Fig 3 Conformational classification (a) all conformations, D_SIA is the distance between HA and SA1, D_NAG is the distance between HA and GlcNAc3; (b) reasonable conformations; (c) binding pose whose ΔG < -41.9 kJ?mol-1 and root-mean-square deviation (RMSD) < 0.4 nm. color online
Fig 4 Energy distribution scatter diagram of HA from 8 fatal H7N9 isolates *The pattern of the pictures is similar to H1 except (f).
Fig 5 Energy distribution scatter diagram of HA from two H7N9 isolates
Fig 6 Affinity-specificity (S) figure green points: H1; red points: H7N9; blue point: wild type H7. color online
1 Taubenberger J. K. ; Morens D. M. Rev. Sci. Tech 2009, 28 (1), 187.
2 dos Reis M. ; Hay A. J. ; Goldstein R. A. J. Mol. Evol. 2009, 69 (4), 333.
3 Neumann G. ; Noda T. ; Kawaoka Y. Nature 2009, 459 (7249), 931.
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.
5 Nakajima K. ; Desselberger U. ; Palese P. Nature 1978, 274, 334.
6 Johnson N. P. ; Mueller J. Bull. Hist. Med 2002, 76 (1), 105.
7 Skehel J. J. ; Wiley D. C. Annu. Rev. Biochem. 2000, 69, 531.
8 Matrosovich M. ; Stech J. ; Klenk H. D. Rev. Sci. Tech. Off. Int.Epiz 2009, 28 (1), 203.
9 Matrosovich M. ; Tuzikov A. ; Bovin N. ; Gambaryan A. ; Klimov A. ; Castrucci M. R. ; Donatelli I. ; Kawaoka Y. J. Virol 2000, 74 (18), 8502.
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.
11 Connor R. J. ; Kawaoka Y. ; Webster R. G. ; Paulson J. C. Virology 1994, 205, 17.
12 Stevens J. ; Blixt O. ; Tumpey T. M. ; Taubenberger J. K. ; Paulson J. C. ; Wilson I. A. Science 2006, 312, 404.
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.
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)
15 Xu R. ; Mcbride R. ; Nycholat C. M. ; Paulson J. C. ; Wilson I. A. J. Virol. 2012, 86 (2), 982.
16 Zhang W. ; Shi Y. ; Qi J. ; Gao F. ; Li Q. ; Fan Z. ; Yan J. ; Gao G. F. J. Virol. 2013, 87 (10), 5949.
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.
18 Eisen M. B. ; Sabesan S. ; Skehel J. J. ; Wiley D. C. Virology 1997, 232 (1), 19.
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.
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.
21 Deng Y. L. ; Yu L. ; Huang Q. Acta Phys.-Chim. Sin 2016, 32 (9), 2355.
21 邓玉玲; 余璐; 黄强. 物理化学学报, 2016, 32 (9), 2355.
22 Goodsell D. S. ; Olson A. J. Proteins:Struct. Funct. Genet. 1990, 8 (3), 195.
23 Huey R. ; Morris G. M. ; Olson A. J. ; Goodsell D. S. J.Comput. Chem. 2007, 28 (6), 1145.
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.
25 Forli S. ; Olson A. J. J. Med. Chem. 2012, 55 (2), 623.
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.
27 Xu R. ; Ekiert D. C. ; Krause J. C. ; Hai R. ; Crowe J. E. ; Jr. Wilson I. A. Science 2010, 328 (5976), 357.
28 Yang H. ; Carney P. ; Stevens J. PLoS Curr. 2010, 2
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.
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.
32 http://www.who.int/influenza/human_animal_interface/influenza_h7n9/RiskAssessment_H7N9_23Feb20115.pdf?ua=1
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.
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.
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