Journal of Molecular Modeling

, Volume 11, Issue 3, pp 248–255 | Cite as

Domain-based homology modeling and mapping of the conformational epitopes of envelope glycoprotein of west nile virus

  • Santhanam Vijayasri
  • Shipra AgrawalEmail author
Original Paper


Knowledge-based modeling has proved significantly accurate for generating the quality models for proteins whose sequence identity with the structurally known targets is greater than or equal to 40%. On the other hand, models obtained for low sequence identities are not reliable. Hence, a reliable and alternative strategy that uses knowledge of domains in the protein can be used to improve the quality of the model generated by the homology method. Here, we report a method for developing a 3D-model for the envelope glycoprotein (Egp) of west nile virus (WNV), using knowledge of structurally conserved functional domains amongst the target sequence (Egp of WNV) and its homologous templates belonging to the same protein family, flaviviridae. This strategy is found to be highly effective in reducing the root mean square deviation (RMSD) value at the Cα positions of the target and its experimental homologues. The 3D structure of a protein is a prerequisite for structure-based drug design as well as for identifying the conformational epitopes that are essential for the designing vaccines. The conformational epitopes are mapped from the 3D structure of Egp of WNV modeled using the concept of an antigenic domain. A total of five such epitope regions/sites have been identified. They have been found distributed in the loop regions (surface) of the whole protein model composed of dimerization, central and immunological domains. These sites are proposed as the binding sites for HLA proteins/B-cell receptors. Binding is required to activate the immune response against WNV.

Figure The conformational epitopes that are distributed in all the domains. They are found out by the algorithm by Kolaskar et al.


West nile virus Flaviviridae Comparative modeling Envelope glycoprotein Domains Genome polyprotein Template structure 


  1. 1.
    Xiong B, Gui C-S, Xu X-Y, Luo C, Chen J, Luo H-B, Chen L-L, Li G-W, Sun T, Yu C-Y, Yue L-D, Duan W-H, Shen J-K, Qin L, Shi T-L, Li Y-X, Chen K-X, Luo X-M, Shen X, Shen J-H, Jiang H-L (2003) Acta Pharmacol Sin 24:497–504Google Scholar
  2. 2.
    Rufino SD, Blundell TL (1994) J Comput Aided Mol Des 8:5–27Google Scholar
  3. 3.
    Chakrabarti S, John J, Sowdhamini R (2004) J Mol Model 10:69–75Google Scholar
  4. 4.
    Sampson BA, Armbrustmacher V (2001) Ann NY Acad Sci 951:172–178Google Scholar
  5. 5.
    Mandl CW, Guirakhoo F, Holzmann H, Heinz FX, Kunz C (1989) J Virol 63:564–571Google Scholar
  6. 6.
    Bairoch A, Apweiler R (1997) J Mol Med 75:312–316Google Scholar
  7. 7.
    Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) J Mol Biol 215:403–410Google Scholar
  8. 8.
    Bateman A, Birney E, Cerruti L, Durbin R, Etwiller L, Eddy SR, Griffiths-Jones S, Howe KL, Marshall M, Sonnhammer EL (2002) Nucleic Acids Res 30:276–280Google Scholar
  9. 9.
    Guex N, Peitsch MC (1997) Electrophoresis 18:2714–2723Google Scholar
  10. 10.
    Kabsch W, Sander C (1983) Biopolymers 22:2577–2637Google Scholar
  11. 11.
    van Gunsteren WF, Berendsen HJC (1990) Angew Chem Int Ed Engl 29:992–1023Google Scholar
  12. 12.
    Peitsch MC (1995) PDB Q Newsl 72:4Google Scholar
  13. 13.
    Luthy R, Bowie JU, Eisenberg D (1992) Nature 356:83–85Google Scholar
  14. 14.
    Colovos C, Yeates TO (1993) Protein Sci 2:1511–1519Google Scholar
  15. 15.
    Laskowski RA, Moss DS, Thornton JM (1993) J Mol Biol 231:1049–1067Google Scholar
  16. 16.
    Hooft RWW, Vriend G, Sander C, Abola EE (1996) Nature 381:272–272Google Scholar
  17. 17.
    Scherret JH, Poidinger M, Mackenzie JS, Broom AK, Deubel V, Lipkin WI, Briese T, Gould EA, Hall RA (2001) Emerg Infect Dis 7(4):697–705Google Scholar
  18. 18.
    Choi J-H, Jung H-Y, Kim H-S, Cho H-G (2000) Bioinformatics 16:1056–1058Google Scholar
  19. 19.
    Kolaskar AS, Kulkarni-Kale U (1999) Virology 261:31–42Google Scholar
  20. 20.
    Rey FA, Heinz FX, Mandl C, Kunz C, Harrison SC (1995) Nature 375:291–298Google Scholar
  21. 21.
    Roehrig JT, Johnson AJ, Hunt AR, Bolin RA, Chu MC (1990) Virology 177:668–675Google Scholar
  22. 22.
    Chothia C, Lesk AM (1986) EMBO J 5:823–826Google Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.Indian Institute of Information TechnologyAllahabad, Deoghat Jhalwa CampusAllahabadIndia

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