Journal of Biomolecular NMR

, Volume 7, Issue 1, pp 72–76 | Cite as

Do NOE distances contain enough information to assess the relative populations of multi-conformer structures?

  • Alexandre M. J. J. Bonvin
  • Axel T. Brünger
Short Communications

Summary

The feasibility of determining the relative populations of multi-conformer structures from NOE-derived distances alone is assessed. Without cross-validation of the NOE restraints, any population ratio can be refined to a similar quality of the fit. Complete cross-validation provides a less biased measure of fit and allows the estimation of the correct population ratio when used in conjunction with very tight distance restraints. With the qualitative distance restraints most commonly used in NMR structure determination, cross-validation is unsuccessful in providing the correct answer. Other experimental sources are therefore needed to determine relative populations of multi-conformer structures.

Keywords

Occupancy refinement Ensemble-averaged NOE restraints Multi-conformer refinement Complete cross-validation Conformational variability Solution structure 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Boelens, R., Koning, T.M.G. and Kaptein, R. (1988) J. Mol. Struct., 173, 299–311.Google Scholar
  2. Bonvin, A.M.J.J., Boelens, R. and Kaptein, R. (1993) In Computer Simulation of Biomolecular Systems: Theoretical and Experimental Applications, Vol. 2 (Eds, Van, Gunsteren, W.F., Weiner, P.K. and Wilkinson, A.J.), ESCOM, Leiden, pp. 407–440.Google Scholar
  3. Bonvin, A.M.J.J. and Brünger, A.T. (1995) J. Mol. Biol., 250, 80–93.Google Scholar
  4. Borgias, B.A., Cochin, M., Kerwood, D.J. and James, T.L. (1990) Prog. NMR Spectrosc., 22, 83–100.Google Scholar
  5. Brünger, A.T. (1993) X-PLOR v. 3.1: A system for X-ray crystallography and NMR, Yale University Press, New Haven, CT.Google Scholar
  6. Brünger, A.T., Clore, M.G., Gronenborn, A.M., Saffrich, R. and Nilges, M. (1993) Science, 261, 328–331.Google Scholar
  7. Burling, F.T. and Brünger, A.T. (1994) Isr. J. Chem., 34, 165–175.Google Scholar
  8. Burling, F.T., Weis, W.I., Flaherty, K.M. and Brünger, A.T. (1996) Science, 271, 72–77.Google Scholar
  9. DeLano, W.L. and Brünger, A.T. (1994) Proteins, 20, 105–123.Google Scholar
  10. Edmonson, S. (1992) J. Magn. Reson. 98, 283–298.Google Scholar
  11. Fennen, J., Torda, A.E. and Van, Gunsteren, W.F. (1995) J. Biomol. NMR, 6, 163–170.Google Scholar
  12. Gerstein, M., Lesk, A.M. and Chothia, C. (1994) Biochemistry, 33, 6739–6749.Google Scholar
  13. Gros, P., Van, Gunsteren, W.F. and Hol, W.G.J. (1990), Science, 249, 1149–1152.Google Scholar
  14. Jeffrey, P.D., Russo, A.A., Polyak, K., Gibbs, E., Hurwitz, J., Massagé, J. and Pavletich, N.P. (1995) Nature, 376, 313–320.Google Scholar
  15. Keepers, J.W. and James, T.L. (1984) J. Magn. Reson., 57, 404–426.Google Scholar
  16. Kim, Y. and Prestegard, J.H. (1989) Biochemistry, 28, 8792–8797.Google Scholar
  17. Kim, Y. and Prestegard, J.H. (1990) Proteins, 8, 377–385.Google Scholar
  18. Koehl, P. and Lefèvre, J.-P. (1990) J. Magn. Reson., 86, 565–583.Google Scholar
  19. Kruse, L.I., DeBrosse, C.W. and Kruse, C.H. (1985) J. Am. Chem. Soc., 107, 5435–5442.Google Scholar
  20. Kuriyan, J., Ösapay, K., Burley, S.K., Brünger, A.T., Hendrickson, W.A. and Karplus, M. (1991) Protein Struct. Funct. Genet., 10, 340–358.Google Scholar
  21. Landis, C.R., Luck, L.L. and Wright, J.M. (1995) J. Magn. Reson. Ser. B, 109, 44–59.Google Scholar
  22. Leeflang, B.R. and Kroon-Batenburg, L.M.J. (1992) J. Biomol. NMR, 2, 495–518.Google Scholar
  23. Liu, H., Banville, D.L., Basus, V.J. and James, T.L. (1995) J. Magn. Reson. Ser. B, 107, 51–59.Google Scholar
  24. Madrid, M., Llinás, E. and Llinás, M. (1991) J. Magn. Reson., 93, 329–346.Google Scholar
  25. Metzler, W.J., Valentine, K., Roebber, M., Friedrichs, M.S., March, D.G. and Mueller, L. (1992) Biochemistry, 31, 5117–5127.Google Scholar
  26. Newman, M., Strzelecka, T., Dorner, L.F., Schildkraut, I. and Aggarwal, A.K. (1995) Science, 269, 656–663.Google Scholar
  27. Nicholson, L.K., Yamazaki, T., Torchia, D.A., Grzesiek, S., Bax, A., Stahl, S.J., Kaufman, J.D., Wingfield, P.T., Lam, P.Y.S., Jadhav, P.K., Hodge, N., Domaille, P.J. and Chang, C.-H. (1995) Nature Struct. Biol., 2, 274–280.Google Scholar
  28. Nilges, M., Clore, G.M. and Gronenborn, A.M. (1988) FEBS Lett., 229, 317–324.Google Scholar
  29. Olejniczak, E.T., GampeJr., R.T. and Fesik, S.W. (1986) J. Magn. Reson., 67, 28–41.Google Scholar
  30. Post, C.B., Meadows, R.P. and Gorenstein, D.G. (1990) J. Am. Chem. Soc., 112, 6796–6803.Google Scholar
  31. Scheek, R.M., Torda, A.E., Kemmink, J. and Van, Gunsteren, W.F. (1991) In Computational Aspects of the Study of Biological Macromolecules by NMR (Eds, Hoch, J.C., Poulsen, F.M. and Redfield, C.), Plenum Press, New York, NY, pp. 209–217.Google Scholar
  32. Schirmer, R.E., Davis, J.P., Noggle, J.H. and Hart, P.A. (1972) J. Am. Chem. Soc., 94, 2561–2572.Google Scholar
  33. Torda, A.E., Scheek, R.M. and Van, Gunsteren, W.F. (1989) Chem. Phys. Lett., 157, 289–294.Google Scholar
  34. Torda, A.E., Brunne, R.M., Huber, T., Kessler, H. and Van, Gunsteren, W.F. (1993) J. Biomol. NMR, 3, 55–66.Google Scholar
  35. Van de Ven, F.J.M., Blommers, M.J.J., Schouten, R.E. and Hilbers, C.W. (1991) J. Magn. Reson., 94, 140–151.Google Scholar

Copyright information

© ESCOM Science Publishers B.V 1996

Authors and Affiliations

  • Alexandre M. J. J. Bonvin
    • 1
    • 2
  • Axel T. Brünger
    • 1
    • 2
  1. 1.The Howard Hughes Medical InstituteYale UniversityNew HavenUSA
  2. 2.Department of Molecular Biophysics and BiochemistryYale UniversityNew HavenUSA

Personalised recommendations