Nuclear Magnetic Resonance (NMR) is a powerful technique for protein structure elucidation as well as for studying protein function and chemistry, e.g. by identifying ligands binding a particular protein or monitoring enzyme catalyzed chemical reactions. However, the absence of an agreed upon measure of the precision of NMR-derived structural models has limited the utility of NMR in structural biology. In particular, the use of NMR structures as targets in the Critical Assessment of Structure Prediction (CASP) competition, requires identification of which regions of an NMR structure are sufficiently well-defined to assess whether predictions of those regions are actually correct or not. CASP10 used the Expanded FindCore method to identify core regions for use in assessing results of structure prediction methods as applied to structures experimentally solved using NMR. This presentation will describe the Expanded FindCore method, and possible variations of it, as well as presenting some interesting observations about the precision of protein structures first made in the process of developing Expanded FindCore. For example, in NMR �ensembles� coordinate variance is higher for carbonyl oxygens than for other backbone heavy atoms. This could reflect the lack of direct NMR constraints on carbonyl oxygen position, however, this same phenomenon is observed with just as high significance, albeit to a lesser degree, in MD trajectories, indicating that the relatively high coordinate variance of carbonyl oxygens, which is not found in crystallographic B factors, is either a deficiency of the force fields used in NMR and MD calculations or is a real physical phenomenon. In general, comparisons between coordinate uncertainties in NMR structures, crystallographic B-factors and coordinate variances in MD trajectories indicate that coordinate uncertainties, reflecting the absence of NMR-derived experimental constraints on structure, may provide just as good of a picture of protein flexibility as do B-factors.

What does the precision of NMR-derived protein structures tell us? Considering the impact of NMR in studying protein chemistry

247th National Meeting (2014)

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