Improving the quality of protein structures derived by NMR spectroscopy.
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.
Spronk
Christian A E M
CA
Department of Biophysical Chemistry, NSR-RIM Center, University of Nijmegen, The Netherlands.
Linge
Jens P
JP
Hilbers
Cornelis W
CW
Vuister
Geerten W
GW
D000818:Animals; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D015847:Interleukin-4 / Q000737:chemistry; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D010940:Plant Proteins / Q000737:chemistry; D011487:Protein Conformation; D015203:Reproducibility of Results; D025801:Ubiquitin / Q000737:chemistry
D010940:Plant Proteins; D025801:Ubiquitin; D015847:Interleukin-4; C024934:crambin protein, Crambe abyssinica