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.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Anil-Kumar, Ernst, R.R. and Wüthrich, K. (1980) Biochem. Biophys. Res. Commun., 95, 1–6.
Antuch, W., Güntert, P. and Wüthrich, K. (1996) Nat. Struct. Biol., 3, 662–665.
Antz, C., Neidig K.P. and Kalbitzer H. R. (1995) J. Biomol. NMR, 5, 287–296.
Bartels, C., Xia, T., Billeter, M., Güntert, P. and Wüthrich, K. (1995) J. Biomol. NMR, 6, 1–10.
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.
Borgias, B.A. and James, T.L. (1988) J. Magn. Reson.,79, 493–513.
Borgias, B.A. and James, T.L. (1990) J. Magn. Reson., 87, 475–487.
Brünger, A.T. (1992)X-PLOR, Version 3.1. A System for X-Ray Crystallography and NMR, Yale University Press, New Haven, USA.
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.
Corne, S.A. and Johnson, P. (1992) Neural Networks, 6, 1023–1032.
Garret, D.S., Powers, R., Gronenborn, A.M. and Glore, G.M. (1991) J. Magn. Reson., 95, 214–220.
Gronwald, W., Kirchhöfer, R., Görler, A., Kremer, W., Ganslmeier, B., Neidig, K.-P. and Kalbitzer, H.R. (2000) J. Biomol. NMR, 17, 137–151.
Güntert, P. and Wüthrich, K. (1992) J. Magn. Reson., 96, 403–407.
Güntert, P., Billeter, M., Ohlenschläger, O., Brown, L.R. and Wüthrich, K. (1998) J. Biomol. NMR, 12, 543–548.
Güntert, P., Braun, W. and Wüthrich, K.(1991) J. Mol. Biol., 217, 517–530.
Güntert, P., Dötsch, V., Wider, G. and Wüthrich K. (1992) J. Biomol.NMR, 2, 619–629.
Güntert, P., Mumenthaler, C. and Wüthrich, K. (1997) J. Mol. Biol., 273, 283–298.
Herrmann, T., Güntert, P. and Wüthrich, K. (2002) J. Mol. Biol., 319, 209–227.
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.
Keepers, J.W. and James, T.L. (1984) J. Magn. Reson., 57, 404–426.
Kleywegt, G.J., Boelens, R. and Kaptein, R. (1990) J. Magn. Reson., 88, 601–608.
Koradi, R., Billeter, M., Engeli, M., Güntert, P. and Wüthrich, K. (1998) J. Magn. Reson. 135, 288–297.
Koradi, R., Billeter, M. and Güntert, P.(2000) Comput. Phys. Commun., 124, 139–147.
Koradi, R., Billeter, M. and Wüthrich, K. (1996) J. Mol. Graph. 14, 51–55.
Luginbühl, P., Güntert, P., Billeter, M. and Wüthrich, K. (1996) J. Biomol. NMR, 8, 136–146.
Mertz, J.E., Güntert, P., Wüthrich, K. and Braun, W. (1991) J. Biomol. NMR, 1, 257–269.
Morris, A.L., MacArthur, M.W., Hutchinson, E.G. and Thornton, J.M. (1992) Proteins, 12, 345–364.
Neidig, K.P., Geyer, M., Görler, A., Antz, C., Saffrich, R., Beneicke, W. and Kalbitzer, H.R. (1995) J. Biomol. NMR, 6, 255–270.
Nilges, M., Habazettl, J., Brünger, A.T. and Holak, T.A. (1991) J. Mol. Biol., 219, 499–510.
Williamson, M., Havel, T. F. and Wüthrich, K. (1985) J. Mol. Biol., 155, 311–319.
Wimmer, R., Herrmann, T., Solioz, M. and Wüthrich, K. (1999) J. Biol. Chem., 274, 22597–22603.
Wüthrich, K. (1986) NMR of Proteins and Nucleic Acids,Wiley, New York, NY.
Wüthrich, K., Billeter, M. and Braun, W. (1983) J. Mol. Biol., 169, 949–961.
Yip, P. and Case, D.A. (1989) J. Magn. Reson., 83, 643–648.
About this article
Cite this article
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
- automated peak picking
- nuclear magnetic resonance
- nuclear Overhauser effect
- protein structure determination