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A Comparative Molecular Similarity Index Analysis (CoMSIA) study identifies an HLA-A2 binding supermotif

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Abstract

The 3D-QSAR CoMSIA technique was applied to a set of 458 peptides binding to the five most widespread HLA-A2-like alleles: A*0201, A*0202, A*0203, A*0206 and A*6802. Models comprising the main physicochemical properties (steric bulk, electron density, hydrophobicity and hydrogen-bond formation abilities) were obtained with acceptable predictivity (q 2 ranged from 0.385 to 0.683). The use of coefficient contour maps allowed an A2-supermotif to be identified based on common favoured and disfavoured areas. The CoMSIA definition for the best HLA-A2 binder is as follows: hydrophobic aromatic amino acid at position 1; hydrophobic bulky side chains at positions 2, 6 and 9; non-hydrogen-bond-forming amino acids at position 3; small aliphatic hydrogen-bond donors at position 4; aliphatic amino acids at position 5; small aliphatic side chains at position 7; and small aliphatic hydrophilic and hydrogen-bond forming amino acids at position 8.

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References

  1. Janeway, C. A. Jr., Travers, P., Walport, M. and Capra, J. D. (Eds.), Immunobiology, Elsevier Science Ltd., London, 1999, pp. 115-162.

    Google Scholar 

  2. Marsh, S. G. E., Bodmer, J. G., Albert, E. D., Bodmer, W. F., Bontrop, R. E., Dupont, B., Erlich H. A., Hansen, J. A., Mach, B., Mayr, W. R., Parham, P., Petersdorf, E. W., Sasazuki, T., Schreuder G. M. Th., Strominger, J. L., Svejgaard, A. and Terasaki, P. I., Eur. J. Immunogenet., 28 (2001) 377.

    Google Scholar 

  3. Sidney, J., Grey, H. M., Kubo, R. T. and Sette, A., Immunol. Today, 17 (1996) 261.

    Google Scholar 

  4. Ellis, J. M., Henson, V., Slack, R., Ng, J., Hartzman, R. J. and Hurley, C. K., Hum. Immunol., 61 (2000) 334.

    Google Scholar 

  5. Sette, A., Livingston, B., McKinney, D., Appella, E., Fikes, J., Sidney, J., Newman, M. and Chesnut, R., Biologicals 29 (2001) 271.

    Google Scholar 

  6. Schönbach, C., Koh, J. L. Y., Sheng, X., Wong, L. and Brusic, V., Nucleic Acids Res. 28 (2000) 222.

    Google Scholar 

  7. Madden, D. R., Annu. Rev. Immunol. 13 (1995) 587.

    Google Scholar 

  8. Madden, D. R., Garboczi, D. N. and Willey, D. C., Cell 75 (1993) 693.

    Google Scholar 

  9. Oprea, T. I. and Waller, C. L., In Lipkowitz, K. B. and Boyd, D. B. (Eds.), Reviews in Computational Chemistry, Volume 11, Wiley-VCH, New York, 1997, pp. 127-182.

    Google Scholar 

  10. Greco, G., Novellino, E. and Martin, Y. C, In Lipkowitz, K. B. and Boyd, D. B. (Eds.), Reviews in Computational Chemistry, Volume 11, Wiley-VCH, New York, 1997, pp. 183-240.

    Google Scholar 

  11. Klebe, G., Abraham, U. and Mietzner, T., J. Med. Chem. 37 (1994) 4130.

    Google Scholar 

  12. Klebe, G. and Abraham, U., J. Comput.-Aid. Mol. Des. 13 (1999) 1.

    Google Scholar 

  13. Böhm, M., Stürzebecher, J. and Klebe, G., J. Med. Chem. 42 (1999) 458.

    Google Scholar 

  14. Doytchinova, I. A. and Flower, D. R., PROTEINS 48 (2002) 505.

    Google Scholar 

  15. Blythe, M. J., Doytchinova, I. A. and Flower, D. R., Bioinformatics 18 (2002) 434.

    Google Scholar 

  16. Ruppert, J., Sidney, J., Celis, E., Kubo, R. T., Grey, H.M. and Sette, A., Cell 74 (1993) 929.

    Google Scholar 

  17. Sette, A., Sidney, J., del Guercio, M.-F., Southwood, S., Ruppert, J., Dalberg, C., Grey, H. M. and Kubo, R. T., Mol. Immunol. 31 (1994) 813.

    Google Scholar 

  18. SYBYL 6.7. Tripos Inc., 1699 Hanley Road, St. Louis, MO 63144.

  19. Doytchinova, I. A. and Flower D. R., J. Med. Chem. 44 (2001) 3572.

    Google Scholar 

  20. Doytchinova, I. A. and Flower D. R., Immunol. Cell Biol. 80 (2002) 270.

    Google Scholar 

  21. Dewar, M. J. S., Zoebisch, E. G., Healy, E.F. and Stewart, J. J. P., J. Am. Chem. Soc. 107 (1985) 3902.

    Google Scholar 

  22. Apex-3D 95.0. User Guide, Biosym/MSI, 9685 Scranton Road, San Diego, CA 92121.

  23. Sidney, J., Southwood, S., Mann, D. L., Fernandez-Vina, M. A., Newman, M. J. and Sette A., Hum. Immunol. 62 (2001) 1200.

    Google Scholar 

  24. Kirksey, T. J., Pogue-Caley, R. R., Frelinger, J. A. and Collins, E. J., J. Biol. Chem. 274 (1999) 37259.

    Google Scholar 

  25. Tourdot, S., Scardino, A., Saloustrou, E., Gross, D. A., Pascolo, S., Cordopatis, P., Lemonnier, F. A. and Kosmatopoulos, K. A., Eur. J. Immunol. 30 (2000) 3411.

    Google Scholar 

  26. Ruppert, J., Sidney, J., Celis, E., Kubo, R. T., Grey, H. M. and Sette, A., Cell 74 (1993) 929.

    Google Scholar 

  27. Parker, K. C., Bednarek, M. A. and Coligan, J.E., J. Immunol. 152 (1994) 163.

    Google Scholar 

  28. Kubo, R. T., Sette, A., Grey, H. M., Appella, E., Sakaguchi, K., Zhu, N.-Z., Arnott, D., Sherman, N., Shabanowitz, J., Michel, H., Bodnar, W. M., Davis, T. A. and Hunt, D. F., J. Immunol. 152 (1994) 3913.

    Google Scholar 

  29. Parker, K. C., Bednarek, M. A., Hull, L. K., Utz, U., Cunningham, B., Zweerink, H. J., Biddison, W. E., Coligan, J. E., J. Immunol. 149 (1992) 3580.

    Google Scholar 

  30. Saper, M. A., Bjorkman, P. J. and Wiley, D. C. J. Mol. Biol. 219 (1991) 277.

    Google Scholar 

  31. Del Guercio, M.-F., Sidney, J., Hermanson, G., Perez, C., Grey, H.M., Kubo, R. T. and Sette, A., J. Immunol. 154 (1995) 685.

    Google Scholar 

  32. Doytchinova, I. A., Blythe, M. J. and Flower, D. R., J Proteome Res. 1 (2002) 263.

    Google Scholar 

  33. Schönbach, C., Koh, J. L. Y., Sheng, X., Wong, L. and Brusic, V., Nucleic Acids Res. 28 (2000) 222.

    Google Scholar 

  34. Sudo, T., Kamikawaji, N., Kimura, A., Date, Y., Savoie, C. J., Nakashima, H., Furuichi, E., Kuhara, S. and Sasazuki, T., J. Immunol. 155 (1995) 4749.

    Google Scholar 

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Authors and Affiliations

  1. Edward Jenner Institute for Vaccine Research, Compton, Berkshire, RG20 7NN, U.K

    Irini A. Doytchinova & Darren R. Flower

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  1. Irini A. Doytchinova
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  2. Darren R. Flower
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Correspondence to Darren R. Flower.

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Doytchinova, I.A., Flower, D.R. A Comparative Molecular Similarity Index Analysis (CoMSIA) study identifies an HLA-A2 binding supermotif. J Comput Aided Mol Des 16, 535–544 (2002). https://doi.org/10.1023/A:1021917203966

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