Journal of Biomolecular NMR

, Volume 22, Issue 3, pp 281–289 | Cite as

Improving the quality of protein structures derived by NMR spectroscopy**

  • Christian A.E.M. Spronk
  • Jens P. Linge
  • Cornelis W. Hilbers
  • Geerten W. Vuister


Biomolecular structures provide the basis for many studies in several research areas such as homology modelling, structure-based drug design and functional genomics. It is an important prerequisite that the structure is reliable in terms of accurate description of the experimental data, and in terms of good quality of local- and overall geometry. Recent surveys indicate that structures solved by NMR-spectroscopy normally are of lower precision than high-resolution X-ray structures. Here, we present a refinement protocol that improves the quality of protein structures determined by NMR-spectroscopy to the level of those determined by high resolution X-ray crystallography in terms of local geometry. The protocol was tested on experimental data of the proteins IL4 and Ubiquitin and on simulated data of the protein Crambin. In almost all aspects, the protocol yielded better results in terms of accuracy and precision. Independent validation of the results for Ubiquitin, using residual dipolar couplings, indicates that the ensemble of NMR structure is substantially improved by the protocol.

NMR structures proteins structure refinement structure validation 


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  1. Brünger, A.T. (1992) X-PLOR. In A system for X-ray Crystallography and NMR, Yale University Press, New Haven, CT.Google Scholar
  2. Cornilescu, G., Marquardt, J.L., Ottiger and Bax, A. (1998) J. Am. Chem. Soc., 120, 6836–6837.Google Scholar
  3. Dingley, A.J. and Grzesiek, S. (1998) J. Am. Chem. Soc., 120, 8293–8297.Google Scholar
  4. Doreleijers, J.F. (1999) PhD thesis, Utrecht University, The Netherlands.Google Scholar
  5. Doreleijers, J.F., Rullmann, J.A. and Kaptein, R. (1998) J. Mol. Biol., 281, 149–164.Google Scholar
  6. Doreleijers, J.F., Vriend, G., Raves, M.L. and Kaptein, R. (1999a) Proteins, 37, 404–416.Google Scholar
  7. Doreleijers, J.F., Raves, M.L., Rullmann, T. and Kaptein, R. (1999b) J. Biomol. NMR, 14, 123–132.Google Scholar
  8. Hooft, R.W., Sander, C. and Vriend, G. (1997) Comput. Appl. Biosci., 13, 425–430.Google Scholar
  9. Jelsch, C., Teeter, M.M., Lamzin, V., Pichon-Pesme, V., Blessing, R.H. and Lecomte, C. (2000) Proc. Natl. Acad. Sci USA, 97, 3171–3176.Google Scholar
  10. Jorgenson, W.L., Chandrasekhan, J., Madura, J., Impley, R.W. and Klein, M.L. (1983) J. Chem. Phys., 79, 926–935.Google Scholar
  11. Kuszewski, J. and Clore, G.M. (2000) J. Magn. Reson., 146, 249–254.Google Scholar
  12. Laskowski, R.A., MacArthur, M.W., Moss, D.S. and Thornton, J.M. (1993) J. Appl. Cryst., 26, 283–291.Google Scholar
  13. Laskowski R.A., Rullmannn J.A., MacArthur M.W., Kaptein R. and Thornton J.M. (1996) J. Biomol. NMR, 8, 477–486.Google Scholar
  14. Linge, J.P. and Nilges, M. (1999) J. Biomol. NMR, 13, 51–59.Google Scholar
  15. MacKerell, Jr. et al., and Karplus, M. (1992) FASEB J., 6, A143.Google Scholar
  16. Nilges, M., Macias, M.J., O'Donoghue, S.I. and Oschkinat, H. (1997) J. Mol. Biol., 269, 408–422.Google Scholar
  17. Powers, R., Garrett, D.S., March, C.J., Frieden, E.A., Gronenborn, A.M. and Clore, G.M. (1992) Science, 256, 1673–1677.Google Scholar
  18. Ryckaert, J.P., Ciccotti, G. and Berendsen, H.J.C. (1977) J. Comp. Phys., 23, 327–341.Google Scholar
  19. Spronk, C.A.E.M., Bonvin, A.M.J.J., Radha, P.K., Melacini, G., Boelens, R. and Kaptein, R. (1999) Structure, 7, 1483–1492.Google Scholar
  20. Tjandra, N. and Bax, A. (1997) J. Magn. Reson., 124, 512–515.Google Scholar
  21. Vijay-Kumar, S., Bugg, C.E., Cook, W.J. (1987) J. Mol. Biol., 194, 531–544.Google Scholar
  22. Vriend, G. (1990) J. Mol. Graph., 8, 52–56.Google Scholar
  23. Walter, M.R., Cook, W.J., Zhao, B.G., Cameron Jr., R.P., Ealick, S.E., Walter Jr., R.L., Reichert, P., Nagabhushan, T.L., Trotta, P.P. and Bugg, C.E. (1992) J. Biol. Chem., 267, 20371–20376.Google Scholar
  24. Wlodaver, A., Pavlovsky, A. and Gustchina, A. (1992) FEBS Lett., 309, 59–64.Google Scholar
  25. Zweckstetter, M. and Bax, A. (2000) J. Am. Chem. Soc., 122, 3791–3792.Google Scholar

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Christian A.E.M. Spronk
    • 1
  • Jens P. Linge
    • 2
  • Cornelis W. Hilbers
    • 1
  • Geerten W. Vuister
    • 1
  1. 1.Department of Biophysical Chemistry, NSR-RIM CenterUniversity of NijmegenThe Netherlands
  2. 2.Unité de Bioinformatique StructuraleInstitut PasteurParisFrance

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