Computational tools have been developed in the last few years, to allow a direct determination of protein structures from NMR data. Numerical calculations with simulated and experimental NMR constraints for distances and torsional angles show that data sets available with present NMR techniques carry enough information to determine reliably the global fold of a small protein. The maximum size of a protein for which the direct method can be applied is not limited by the computational tools but rather by the resolution of the two-dimensional spectra. A general estimate of the maximum size would be a molecular weight of about 10,000 (Markley et al. 1984), but parts of larger proteins might be accessible with the method. Effort for improvement of the NMR structures should be concentrated more on the local conformation rather than the global features. The r.m.s. D values for variations of the polypeptide backbone fold are on the order of 1.5-2 A for several of the studied proteins, indicating that the global structure is well determined by the present NMR data and their interpretation. The local structures are sometimes rather poor, with standard deviations for the backbone torsion angles of about 50 degrees. Possible improvements would be stereospecific resonance assignments of individual methylene protons and individual assignments of the methyl groups of the branched side-chains. Accurate estimates of the short-range NOE distance constraints by calibrating the distance constraints, including segmental flexibility effects, and combined use of distance geometry, energy minimization and molecular dynamics calculations, are further tools for improving the structures.
|Original language||English (US)|
|Number of pages||43|
|Journal||Quarterly Reviews of Biophysics|
|State||Published - May 1987|
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