Different biophysical approaches to structure and dynamics have inherent advantages and disadvantages. X-ray crystallography has no limitation on the size of a macromolecule or complex, but requires the formation of high quality crystals of a macromolecule of sufficient size for data collection. Solution-state NMR only requires that the molecule be soluble at sufficient concentration for data collection, but becomes increasingly difficult for biomolecules over 30 kDa so that a practical size limitation is placed on full structure determinations.
Solid-state NMR (ssNMR) does not require that the sample be soluble or form a crystal, and the approach can be used to study molecules larger than 100 kD (Tycko, 2001). However, with ssNMR comes a new set of limitations and problems that need to be overcome.
In solution NMR, the molecules in the sample tumble randomly at rates fast enough to average out anisotropic chemical shifts and couplings. The advantage of this inherent isotropy (same in all directions) is that the NMR spectrum appears as a set of narrow, well defined lines with sharp transitions. The disadvantage of this is that orientation-dependent (anisotropic) information is lost. In solution state NMR, some of this information can be regained by orienting the molecules partially, for example by adding phage particles that line up in the magnetic field.
In solids, all of the anisotropic features are present and potentially limit the features observable in NMR spectra of biological macromolecules. Fortunately, NMR spectroscopists have found ways of suppressing and controlling anisotropic interactions.
E. R. Andrew and I. J. Lowe showed in the late 1950s that certain kinds of anisotropic interactions could be controlled by a method called magic angle spinning - MAS (Andrew et al, 1958, Lowe, 1959). First, the sample is ground into a fine powder and packed into a cylinder. Then, it is placed in a special probe/rotor so that it will be oriented at 54.74° to the magnetic field and spun.
Unfortunately, the sample needs to be spun faster (in Hz - rotations per second) than the magnitude of the dipolar coupling (also measured in Hz), which can be on the order of thousands or even hundreds of thousands of cycles per second.
Designing an NMR probe to do this is, to say the least, problematic. In general, the engineering requirements of solid-state NMR tend to be much greater (and more expensive) than for solution state, so there are not nearly as many research efforts using it.
Magic-angle spinning can be combined with multiple-pulse sequences for even greater control of the nuclear interactions that can occur in an experiment. Quite a lot of information can be obtained this way, but again, timing rotational position and frequency with individual electro-magnetic pulses is technically very challenging.
It is also possible to perform NMR experiments on a single crystal. These experiments are performed in a similar manner to x-ray crystallography, where the orientation of the crystal is known and then it is rotated about the x, y, and z, axes.
Introduction to Solid-State NMR - A tutorial by Rob Schurko from the University of Windsor
RCN - Research Coordination Network NMR of Biological Solids
Chemical Shift Tensor Conventions = converters between Standard, Haeberlen, and Herzfeld-Berger tensor conventions.
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Cynthia J. Jameson; "Reply to 'conventions for tensor quantities used in nuclear magnetic resonance, nuclear quadrupole resonance and electron spin resonance spectroscopy"; Solid State Nuclear Magnetic Resonance 11, 265-268, (1998)
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