Advertisement

Journal of Biomolecular NMR

, Volume 20, Issue 1, pp 15–21 | Cite as

Structure prediction of protein complexes by an NMR-based protein docking algorithm

  • Oliver Kohlbacher
  • Andreas Burchardt
  • Andreas Moll
  • Andreas Hildebrandt
  • Peter Bayer
  • Hans-Peter Lenhof
Article

Abstract

Protein docking algorithms can be used to study the driving forces and reaction mechanisms of docking processes. They are also able to speed up the lengthy process of experimental structure elucidation of protein complexes by proposing potential structures. In this paper, we are discussing a variant of the protein-protein docking problem, where the input consists of the tertiary structures of proteins A and B plus an unassigned one-dimensional 1H-NMR spectrum of the complex AB. We present a new scoring function for evaluating and ranking potential complex structures produced by a docking algorithm. The scoring function computes a `theoretical' 1H-NMR spectrum for each tentative complex structure and subtracts the calculated spectrum from the experimental one. The absolute areas of the difference spectra are then used to rank the potential complex structures. In contrast to formerly published approaches (e.g. [Morelli et al. (2000) Biochemistry, 39, 2530–2537]) we do not use distance constraints (intermolecular NOE constraints). We have tested the approach with four protein complexes whose three-dimensional structures are stored in the PDB data bank [Bernstein et al. (1977)] and whose 1H-NMR shift assignments are available from the BMRB database. The best result was obtained for an example, where all standard scoring functions failed completely. Here, our new scoring function achieved an almost perfect separation between good approximations of the true complex structure and false positives.

NMR shift prediction protein docking structure prediction 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bernstein, F., Koetzle, T., Williams, G., Meyer Jr., E., Brice, M., Rodgers, J., Kennard, O., Shimanouchi, T. and Tasumi, M. (1977) J. Mol. Biol., 112, 535-542Google Scholar
  2. Betts, M.J. and Sternberg, M.J.E. (1999) Protein Eng., 12, 271-283.Google Scholar
  3. Connolly, M.L. (1986) Biopolymers, 25, 1229-1247.Google Scholar
  4. Cornell, W.D., Cieplak, P., Bayly, C.I., Gould, I.R., Merz Jr., K.M., Ferguson, D.M., Spellmeyer, D.C., Fox, T., Caldwell, J.W. and Kollman, P.A. (1995) J. Am. Chem. Soc., 117, 5179-5197.Google Scholar
  5. Elshorst, B., Hennig, M., Foersterling, H., Diener, A., Maurer, M., Schwalbe, H., Griesinger, C., Krebs, J., Schmid, H., Vorherr, T. and Carafoli, E. (1999) Biochemistry, 38, 12320-12332.Google Scholar
  6. Fischer, D., Lin, S.L., Wolfson, H.J. and Nussinov, R. (1995) J. Mol. Biol., 248, 459-477.Google Scholar
  7. Haigh, C.W. and Mallion, R.B. (1972) Org. Magn. Reson., 4, 203-228.Google Scholar
  8. Hoffmann, D., Kramer, B., Washio, T., Steinmetzer, T., Rarey, M. and Lengauer, T. (1999) J. Med. Chem., 42, 4422-4433.Google Scholar
  9. Jackson, R.M., Gabb, H.A. and Sternberg, M.J.E. (1998) J. Mol. Biol., 276, 265-285.Google Scholar
  10. Jackson, R.M. and Sternberg, M.J.E. (1995) J. Mol. Biol., 250, 258-275.Google Scholar
  11. Johnson, C.E. and Bovey, F.A. (1958) Chem. Phys., 29, 1012-1030.Google Scholar
  12. Katchalski-Katzir, E., Shariv, I., Eisenstein, M., Friesem, A.A., Afalo, C. and Vakser, I.A. (1992) Proc. Natl. Acad. Sci. USA, 89, 2195-2199.Google Scholar
  13. Kohlbacher, O. and Lenhof, H.-P. (2000) Bioinformatics, 16, 815-824.Google Scholar
  14. Lengauer, T. and Rarey, M. (1996) Curr. Opin. Struct. Biol., 6, 402-406.Google Scholar
  15. Lenhof, H.-P. (1995) In: Bioinformatics: From nucleic acids and proteins to cell metabolism (Eds, Schomburg, D. and Lessel, U.), GBF Monographs Volume 18, pp. 125-139.Google Scholar
  16. Lenhof, H.-P. (1997) In: Proceedings of the First Annual International Conference on Computational Molecular Biology RECOMB 97, pp. 182-191.Google Scholar
  17. McConnell, H.M. (1957) J. Chem. Phys., 27, 227-229.Google Scholar
  18. Meyer, M., Wilson, P. and Schomburg, D. (1996) J. Mol. Biol., 264, 199-210.Google Scholar
  19. Morelli, X., Dolla, A., Czjzek, M., Palma, N., Blasco, F., Krippahl, L., Moura, J.J.G. and Guerlesquin, F. (2000) Biochemistry, 39, 2530-2537.Google Scholar
  20. Norel, R., Lin, S.L., Wolfson, H.J. and Nussinov, R. (1994) Biopolymers, 34, 933-940.Google Scholar
  21. Osawa, M., Tokumitsu, H., Swindells, M.B., Kurihara, H., Orita, M., Shibanuma, T., Furuya, T. and Ikura, M. (1999) Nat. Struct. Biol., 6, 819-824.Google Scholar
  22. Polshakov, V.I., Morgan, W.D., Birdsall, B. and Feeney, J. (1999) J. Biomol. NMR, 14, 115-122.Google Scholar
  23. Rarey, M., Kramer, B., Lengauer, T. and Klebe, G. (1997) J. Mol. Biol., 261, 470-489.Google Scholar
  24. Rustandi, R.R., Drohat, A.C., Baldisseri, D.M., Wilder, P.T. and Weber, D.J. (1998) Biochemistry, 37, 1951-1960.Google Scholar
  25. Sandak, B., Nussinov, R. and Wolfson, H.J. (1998) J. Comput. Biol., 5, 631-654.Google Scholar
  26. Seavey, B.R., Farr, E.A., Westler, W.M. and Markley, J. (1991) J. Biomol. NMR, 1, 217-236.Google Scholar
  27. Shoichet, B.K. and Kuntz, I.D. (1991) J. Mol. Biol., 221, 79-102.Google Scholar
  28. Sternberg, M.J.E., Gabb, H.A. and Jackson, R.M. (1998) Curr. Opin. Struct. Biol., 8, 250-256.Google Scholar
  29. Totrov, M. and Abagyan, R. (1994) Nat. Struct. Biol., 1, 259-263.Google Scholar
  30. Trosset, J.-Y. and Scheraga, H.A. (1999) J. Comput. Chem., 20, 412-427.Google Scholar
  31. Wang, J.-M., Xu, X.-J. and Jiang, F. (1998) In: Proceedings of the Fourth Chinese Peptide Symposium (Eds, Xu, X.-J., Ye, Y.-H. and Tam, J.P.), Kluwer, Dordrecht, pp. 106-108.Google Scholar
  32. Weng, Z., Vajda, S. and Delisi, C. (1996) Protein Sci., 5, 614-626.Google Scholar
  33. Williamson, M.P. and Asakura, T. (1993) J. Magn. Reson., B101, 63-71.Google Scholar
  34. Zhang, C., Cornette, J.L. and DeLisi, C. (1997) Protein Sci., 6, 1059-1064.Google Scholar

Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • Oliver Kohlbacher
  • Andreas Burchardt
  • Andreas Moll
  • Andreas Hildebrandt
  • Peter Bayer
  • Hans-Peter Lenhof

There are no affiliations available

Personalised recommendations