Protein NMR structure determination with automated NOE-identification in the NOESY spectra using the new software ATNOS

Abstract

Novel algorithms are presented for automated NOESY peak picking and NOE signal identification in homonuclear 2D and heteronuclear-resolved 3D [1H,1H]-NOESY spectra during de novoprotein structure determination by NMR, which have been implemented in the new software ATNOS (automated NOESY peak picking). The input for ATNOS consists of the amino acid sequence of the protein, chemical shift lists from the sequence-specific resonance assignment, and one or several 2D or 3D NOESY spectra. In the present implementation, ATNOS performs multiple cycles of NOE peak identification in concert with automated NOE assignment with the software CANDID and protein structure calculation with the program DYANA. In the second and subsequent cycles, the intermediate protein structures are used as an additional guide for the interpretation of the NOESY spectra. By incorporating the analysis of the raw NMR data into the process of automated de novoprotein NMR structure determination, ATNOS enables direct feedback between the protein structure, the NOE assignments and the experimental NOESY spectra. The main elements of the algorithms for NOESY spectral analysis are techniques for local baseline correction and evaluation of local noise level amplitudes, automated determination of spectrum-specific threshold parameters, the use of symmetry relations, and the inclusion of the chemical shift information and the intermediate protein structures in the process of distinguishing between NOE peaks and artifacts. The ATNOS procedure has been validated with experimental NMR data sets of three proteins, for which high-quality NMR structures had previously been obtained by interactive interpretation of the NOESY spectra. The ATNOS-based structures coincide closely with those obtained with interactive peak picking. Overall, we present the algorithms used in this paper as a further important step towards objective and efficient de novoprotein structure determination by NMR.

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References

  1. Anil-Kumar, Ernst, R.R. and Wüthrich, K. (1980) Biochem. Biophys. Res. Commun., 95, 1–6.

    PubMed  Google Scholar 

  2. Antuch, W., Güntert, P. and Wüthrich, K. (1996) Nat. Struct. Biol., 3, 662–665.

    PubMed  Google Scholar 

  3. Antz, C., Neidig K.P. and Kalbitzer H. R. (1995) J. Biomol. NMR, 5, 287–296.

    Google Scholar 

  4. Bartels, C., Xia, T., Billeter, M., Güntert, P. and Wüthrich, K. (1995) J. Biomol. NMR, 6, 1–10.

    Google Scholar 

  5. Boelens, R., Koning, T.M.G., van der Marel, G.A., van Boom, J.H.and Kaptein, R. (1989) J. Magn. Reson., 82, 290–308.

    Google Scholar 

  6. Borgias, B.A. and James, T.L. (1988) J. Magn. Reson.,79, 493–513.

    Google Scholar 

  7. Borgias, B.A. and James, T.L. (1990) J. Magn. Reson., 87, 475–487.

    Google Scholar 

  8. Brünger, A.T. (1992)X-PLOR, Version 3.1. A System for X-Ray Crystallography and NMR, Yale University Press, New Haven, USA.

    Google Scholar 

  9. Brünger, A.T., Adams, P.D., Clore, G.M., DeLano, W.L., Gros, P., Grosse-Kunstleve, R.W., Jiang, J.S., Kuszewski, J., Nilges, M., Pannu, N.S., Read, R.J., Rice, L.M., Simonson, T. and Warren, G.L. (1998) Acta Crystallogr., D54, 905–921.

    Google Scholar 

  10. Corne, S.A. and Johnson, P. (1992) Neural Networks, 6, 1023–1032.

    Google Scholar 

  11. Garret, D.S., Powers, R., Gronenborn, A.M. and Glore, G.M. (1991) J. Magn. Reson., 95, 214–220.

    Google Scholar 

  12. Gronwald, W., Kirchhöfer, R., Görler, A., Kremer, W., Ganslmeier, B., Neidig, K.-P. and Kalbitzer, H.R. (2000) J. Biomol. NMR, 17, 137–151.

    PubMed  Google Scholar 

  13. Güntert, P. and Wüthrich, K. (1992) J. Magn. Reson., 96, 403–407.

    Google Scholar 

  14. Güntert, P., Billeter, M., Ohlenschläger, O., Brown, L.R. and Wüthrich, K. (1998) J. Biomol. NMR, 12, 543–548.

    Google Scholar 

  15. Güntert, P., Braun, W. and Wüthrich, K.(1991) J. Mol. Biol., 217, 517–530.

    PubMed  Google Scholar 

  16. Güntert, P., Dötsch, V., Wider, G. and Wüthrich K. (1992) J. Biomol.NMR, 2, 619–629.

    Google Scholar 

  17. Güntert, P., Mumenthaler, C. and Wüthrich, K. (1997) J. Mol. Biol., 273, 283–298.

    PubMed  Google Scholar 

  18. Herrmann, T., Güntert, P. and Wüthrich, K. (2002) J. Mol. Biol., 319, 209–227.

    PubMed  Google Scholar 

  19. Horst, R., Damberger, F., Luginbühl, P., Güntert, P., Peng, G., Nikonova, L., Leal, W.S. and Wüthrich, K. (2001). Proc. Natl. Acad. Sci. USA, 98, 14374–14379.

    PubMed  Google Scholar 

  20. Keepers, J.W. and James, T.L. (1984) J. Magn. Reson., 57, 404–426.

    Google Scholar 

  21. Kleywegt, G.J., Boelens, R. and Kaptein, R. (1990) J. Magn. Reson., 88, 601–608.

    Google Scholar 

  22. Koradi, R., Billeter, M., Engeli, M., Güntert, P. and Wüthrich, K. (1998) J. Magn. Reson. 135, 288–297.

    PubMed  Google Scholar 

  23. Koradi, R., Billeter, M. and Güntert, P.(2000) Comput. Phys. Commun., 124, 139–147.

    Google Scholar 

  24. Koradi, R., Billeter, M. and Wüthrich, K. (1996) J. Mol. Graph. 14, 51–55.

    PubMed  Google Scholar 

  25. Luginbühl, P., Güntert, P., Billeter, M. and Wüthrich, K. (1996) J. Biomol. NMR, 8, 136–146.

    PubMed  Google Scholar 

  26. Mertz, J.E., Güntert, P., Wüthrich, K. and Braun, W. (1991) J. Biomol. NMR, 1, 257–269.

    PubMed  Google Scholar 

  27. Morris, A.L., MacArthur, M.W., Hutchinson, E.G. and Thornton, J.M. (1992) Proteins, 12, 345–364.

    PubMed  Google Scholar 

  28. Neidig, K.P., Geyer, M., Görler, A., Antz, C., Saffrich, R., Beneicke, W. and Kalbitzer, H.R. (1995) J. Biomol. NMR, 6, 255–270.

    Google Scholar 

  29. Nilges, M., Habazettl, J., Brünger, A.T. and Holak, T.A. (1991) J. Mol. Biol., 219, 499–510.

    PubMed  Google Scholar 

  30. Williamson, M., Havel, T. F. and Wüthrich, K. (1985) J. Mol. Biol., 155, 311–319.

    Google Scholar 

  31. Wimmer, R., Herrmann, T., Solioz, M. and Wüthrich, K. (1999) J. Biol. Chem., 274, 22597–22603.

    PubMed  Google Scholar 

  32. Wüthrich, K. (1986) NMR of Proteins and Nucleic Acids,Wiley, New York, NY.

    Google Scholar 

  33. Wüthrich, K., Billeter, M. and Braun, W. (1983) J. Mol. Biol., 169, 949–961.

    PubMed  Google Scholar 

  34. Yip, P. and Case, D.A. (1989) J. Magn. Reson., 83, 643–648.

    Google Scholar 

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Correspondence to Kurt Wüthrich.

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Herrmann, T., Güntert, P. & Wüthrich, K. Protein NMR structure determination with automated NOE-identification in the NOESY spectra using the new software ATNOS. J Biomol NMR 24, 171–189 (2002). https://doi.org/10.1023/A:1021614115432

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  • ATNOS
  • automated peak picking
  • CANDID
  • DYANA
  • nuclear magnetic resonance
  • nuclear Overhauser effect
  • protein structure determination