Abstract
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.
Similar content being viewed by others
References
Brünger, A.T. (1992) X-PLOR. In A system for X-ray Crystallography and NMR, Yale University Press, New Haven, CT.
Cornilescu, G., Marquardt, J.L., Ottiger and Bax, A. (1998) J. Am. Chem. Soc., 120, 6836–6837.
Dingley, A.J. and Grzesiek, S. (1998) J. Am. Chem. Soc., 120, 8293–8297.
Doreleijers, J.F. (1999) PhD thesis, Utrecht University, The Netherlands.
Doreleijers, J.F., Rullmann, J.A. and Kaptein, R. (1998) J. Mol. Biol., 281, 149–164.
Doreleijers, J.F., Vriend, G., Raves, M.L. and Kaptein, R. (1999a) Proteins, 37, 404–416.
Doreleijers, J.F., Raves, M.L., Rullmann, T. and Kaptein, R. (1999b) J. Biomol. NMR, 14, 123–132.
Hooft, R.W., Sander, C. and Vriend, G. (1997) Comput. Appl. Biosci., 13, 425–430.
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.
Jorgenson, W.L., Chandrasekhan, J., Madura, J., Impley, R.W. and Klein, M.L. (1983) J. Chem. Phys., 79, 926–935.
Kuszewski, J. and Clore, G.M. (2000) J. Magn. Reson., 146, 249–254.
Laskowski, R.A., MacArthur, M.W., Moss, D.S. and Thornton, J.M. (1993) J. Appl. Cryst., 26, 283–291.
Laskowski R.A., Rullmannn J.A., MacArthur M.W., Kaptein R. and Thornton J.M. (1996) J. Biomol. NMR, 8, 477–486.
Linge, J.P. and Nilges, M. (1999) J. Biomol. NMR, 13, 51–59.
MacKerell, Jr. et al., and Karplus, M. (1992) FASEB J., 6, A143.
Nilges, M., Macias, M.J., O'Donoghue, S.I. and Oschkinat, H. (1997) J. Mol. Biol., 269, 408–422.
Powers, R., Garrett, D.S., March, C.J., Frieden, E.A., Gronenborn, A.M. and Clore, G.M. (1992) Science, 256, 1673–1677.
Ryckaert, J.P., Ciccotti, G. and Berendsen, H.J.C. (1977) J. Comp. Phys., 23, 327–341.
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.
Tjandra, N. and Bax, A. (1997) J. Magn. Reson., 124, 512–515.
Vijay-Kumar, S., Bugg, C.E., Cook, W.J. (1987) J. Mol. Biol., 194, 531–544.
Vriend, G. (1990) J. Mol. Graph., 8, 52–56.
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.
Wlodaver, A., Pavlovsky, A. and Gustchina, A. (1992) FEBS Lett., 309, 59–64.
Zweckstetter, M. and Bax, A. (2000) J. Am. Chem. Soc., 122, 3791–3792.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Spronk, C.A., Linge, J.P., Hilbers, C.W. et al. Improving the quality of protein structures derived by NMR spectroscopy** . J Biomol NMR 22, 281–289 (2002). https://doi.org/10.1023/A:1014971029663
Issue Date:
DOI: https://doi.org/10.1023/A:1014971029663