The influence of internuclear spatial distribution and instrument noise on the precision of distances determined by solid state NMR of isotopically enriched proteins.

The relative merits of different isotopic enrichment strategies that might be used in solid state NMR protein structure determinations are explored. The basis for comparison of these merits is the determination of the relative uncertainties in rates measured by a generalized dipolar recoupling experiment. The different schemes considered use (13)C, (15)N and (2)H labeling of ubiquitin with homonuclear magnetization-transfer type experiments under magic-angle spinning (MAS). Specific attention is given to the sensitivity of the predicted relative precisions to variation in natural nuclear density distribution and noise levels. A framework is suggested to gauge the precision of measurement of a given dipolar coupling constant, and the potential for a set of such measurements to constrain structure calculations is explored. The distribution of nuclei in homonuclear (15)N and (1)H dipolar recoupling spin-exchange experiments appear to provide the most promising tertiary structure information for uniformly labeled ubiquitin.