Structure determination of symmetric oligomeric proteins by NMR spectroscopy presents a problem, since the degenerate chemical shifts of each monomer do not allow to distinguish between intra- and inter-monomer NOE signals. Thus, information about the aggregation state of a protein can be ascertained using alternative approaches:

¹H, ¹³C, or ¹⁵N chemical shift changes upon dilution. Comparison with chemical shift values for nuclei close to the monomer state.

From diffusion coefficient measurements

From correlation times and relaxation behavior.

Use of isotope-filtering methods combined with asymmetric labeling ( 99JB39). For instance, mixing isotopically labelled and unlabelled monomers within the symmetric oligomers ( 91BIO6332). However, such methods are useful for dimers but not for higher-order oligomers.

The symmetry-ADR computational method ( 93PROT297-17 and 93PROE557-3). Applications have been reported in 96JB193, 94NAT877, 00JB93.

The problems associated with the calculation of structures of symmetric oligomers from NMR data have been reported ( B99KRIS131). Also see Oligomeric Proteins