Journal of Biomolecular NMR

, Volume 25, Issue 3, pp 225–234 | Cite as

The precision of NMR structure ensembles revisited

  • Chris A.E.M. Spronk
  • Sander B. Nabuurs
  • Alexandre M.J.J. Bonvin
  • Elmar Krieger
  • Geerten W. Vuister
  • Gert VriendEmail author


Biomolecular structures provide the basis for many studies in research areas such as structure-based drug design and homology modeling. In order to use molecular coordinates it is important that they are reliable in terms of accurate description of the experimental data and in terms of the overall and local geometry. Besides these primary quality criteria an indication is needed for the uncertainty in the atomic coordinates that may arise from the dynamic behavior of the considered molecules as well as from experimental- and computational procedures.

In contrast to the crystallographic B-factor, a good measure for the uncertainty in NMR-derived atomic coordinates is still not available. It has become clear in recent years that the widely used atomic Root Mean Square Deviation (RMSD), which is a measure for the precision of the data, overestimates the accuracy of NMR structure ensembles and therefore is a problematic measure for the uncertainty in the atomic coordinates.

In this study we report a method that yields a more realistic estimate of the uncertainty in the atomic coordinates by maximizing the RMSD of an ensemble of structures, while maintaining the accordance with the experimentally derived data. The results indicate that the RMSD of most NMR structure ensembles can be significantly increased compromising neither geometric quality nor NMR data. This maximized RMSD therefore seems a better estimate of the true uncertainty in the atomic coordinates.

accuracy NMR structures precision structure refinement structure validation 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Allen, F.H., Kennard, O. and Taylor, R. (1983) Acc. Chem. Res., 16, 146-153.Google Scholar
  2. 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 Cryst., D54, 905-921.Google Scholar
  3. Brünger, A.T., Clore, G.M., Gronenborn, A.M., Saffrich, R. and Nilges, M. (1993) Science, 261, 328-331.Google Scholar
  4. Chalaoux, F.R., O’Donoghue, S.I. and Nilges, M. (1999) Proteins, 34, 453-463.Google Scholar
  5. Clore, G.M., Robien, M.A. and Gronenborn, A.M. (1993) J. Mol. Biol., 231, 82-102.Google Scholar
  6. Cornilescu, G., Marquardt, J., Ottiger, M. and Bax, A. (1998) J. Am. Chem. Soc., 120, 6836-6837.Google Scholar
  7. de Groot, B.L., van Aalten, D.M., Scheek, R.M., Amadei, A., Vriend, G. and Berendsen, H.J. (1997) Proteins, 29, 240-251.Google Scholar
  8. Doreleijers, J.F., Vriend, G., Raves, M.L. and Kaptein, R. (1999) Proteins, 37, 404-416.Google Scholar
  9. Engh, R.A. and Huber, R. (1991) Acta Cryst., A47, 392-400.Google Scholar
  10. Gronenborn, A.M. and Clore, G.M. (1995) Crit. Rev. Biochem. Mol. Biol., 30, 351-385.Google Scholar
  11. Gronenborn, A.M., Filpula, D.R., Essig, N.Z., Achari, A., Whitlow, M., Wingfield, P.T. and Clore, G.M. (1991) Science, 253, 657-661.Google Scholar
  12. Havel, T.F. and Wüthrich, K. (1985) J. Mol. Biol., 182, 281-294.Google Scholar
  13. Hooft, R.W., Sander, C. and Vriend, G. (1996) J. Appl. Cryst., 29, 714-716.Google Scholar
  14. Hooft, R.W., Sander, C. and Vriend, G. (1997) Comput. Appl. Biosci., 13, 425-430.Google Scholar
  15. Horstink, L.L.M., Nilges, M. and Hilbers, C.W. 2000. Internal Dynamics in Single-Stranded DNA Binding Proteins, Ph.D. Thesis, University of Nijmegen, The Netherlands, pp. 67-80.Google Scholar
  16. 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
  17. Jorgensen, W.L. and Tirado-Rives, J. (1988) J. Am. Chem. Soc., 110, 1657-1666.Google Scholar
  18. Jorgensen, W.L., Chandrasekhan, J., Madura, J., Impley, R.W. and Klein, M.L. (1983) J. Chem. Phys., 79, 926-935.Google Scholar
  19. Kabsch, W. and Sander, C. (1983) Biopolymers, 22, 2577-2637.Google Scholar
  20. Koradi, R., Billeter, M. and Wüthrich, K. (1996) J. Mol. Graph., 14, 51-55.Google Scholar
  21. Kuszewski, J., Gronenborn, A.M. and Clore, G.M. (1999) J. Am. Chem. Soc., 121, 2337-2338.Google Scholar
  22. Laskowski, R.A., MacArthur, M.W., Moss, D.S. and Thornton, J.M. (1993) J. Appl. Cryst., 26, 283-291.Google Scholar
  23. Laskowski, R.A., Rullmannn, J.A., MacArthur, M.W., Kaptein, R. and Thornton, J.M. (1996) J. Biomol. NMR, 8, 477-486.Google Scholar
  24. Linge, J.P. and Nilges, M. (1999) J. Biomol. NMR, 13, 51-59.Google Scholar
  25. Linge, J.P., O’Donoghue, S.I. and Nilges, M. (2001) Meth. Enzymol., 339, 71-90.Google Scholar
  26. Linge, J.P., Williams, M.A., Spronk, C.A.E.M., Bonvin, A.M.J.J. and Nilges, M. (2003) Proteins, 50, 496-506.Google Scholar
  27. Lippens, G., Najib, J., Wodak, S.J. and Tartar, A. (1995) Biochemistry, 34, 13-21.Google Scholar
  28. MacArthur, M.W. and Thornton, J.M. (1996) J. Mol. Biol., 264, 1180-1195.Google Scholar
  29. Nilges, M., Macias, M.J., O’Donoghue, S.I. and Oschkinat, H. (1997) J. Mol. Biol., 269, 408-422.Google Scholar
  30. Pfeiffer, S., Karimi-Nejad, Y. and Rüterjans, H. (1997) J. Mol. Biol., 266, 400-423.Google Scholar
  31. Scheek, M., van Nuland, N.A.J., de Groot, B.L. and Amadei, A. (1995) J. Biomol. NMR, 6, 106-111.Google Scholar
  32. Sprangers, R., Bottomley, M.J., Linge, J.P., Schultz, J., Nilges, M. and Sattler, M. (2000) J. Biomol. NMR, 16, 47-58.Google Scholar
  33. Spronk, C.A.E.M., Linge, J.P., Hilbers, C.W. and Vuister, G.W. (2002) J. Biomol. NMR, 22, 281-289.Google Scholar
  34. Spronk, C.A.E.M., Tessari, M., Kaan, A.M., Jansen, J.F., Vermeulen, M., Stunnenberg, H.G. and Vuister, G.W. (2000) Nat. Struct. Biol., 7, 1100-1104.Google Scholar
  35. Tjandra, N., Marquardt, J. and Clore, G.M. (2000) J. Magn. Reson., 142, 393-396.Google Scholar
  36. Torda, A.E., Scheek, R.M. and van Gunsteren, W.F. (1990) J. Mol. Biol., 214, 223-235.Google Scholar
  37. Vriend, G. (1990) J. Mol. Graph., 8, 52-56.Google Scholar
  38. Wilson, K.S., Butterworth, S., Dauter, Z., Lamzin, V.S., Walsh, M., Wodak, S., Pontius, J., Richelle, J., Vaguine, A., Sander, C., Hooft, R.W.W., Vriend, G., Thornton, J.M., Laskowski, R.A., MacArthur, M.W., Dodson, E.J., Murshudov, G., Oldfield, T.J., Kaptein, R. and Rullmann, J.A.C. (1998) J. Mol. Biol., 276, 417-436.Google Scholar
  39. Zhao, D. and Jardetzky, O. (1994) J. Mol. Biol., 239, 601-607.Google Scholar

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • Chris A.E.M. Spronk
    • 1
  • Sander B. Nabuurs
    • 1
  • Alexandre M.J.J. Bonvin
    • 2
  • Elmar Krieger
    • 1
  • Geerten W. Vuister
    • 3
  • Gert Vriend
    • 1
  1. 1.Centre for Molecular and Biomolecular InformaticsUniversity of NijmegenThe Netherlands
  2. 2.Department of NMR-spectroscopyUniversity of UtrechtThe Netherlands
  3. 3.Department of Biophysical ChemistryUniversity of NijmegenThe Netherlands

Personalised recommendations