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
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.
Solid-state NMR draft deposition specification:
Introduction to Solid-State NMR
- A tutorial by Rob Schurko from the University of Windsor
- Research Coordination Network NMR of Biological Solids
Chemical Shift Tensor Conventions
= converters between Standard, Haeberlen, and Herzfeld-Berger tensor conventions.
Papers concerning the Mathematical Tools of NMR
Smith, S. A.,Palke, W. E., and Gerig, J. T; "The Hamiltonians of NMR Part I";
Concepts in Magnetic Resonace 4, 107-144, (1992)
Smith, S. A.,Palke, W. E., and Gerig, J. T; "The Hamiltonians of NMR Part II";
Concepts in Magnetic Resonace 4, 181-204, (1992)
Smith, S. A.,Palke, W. E., and Gerig, J. T; "The Hamiltonians of NMR Part III";
Concepts in Magnetic Resonace 5, 151-177, (1993)
Smith, S. A.,Palke, W. E., and Gerig, J. T; "The Hamiltonians of NMR Part IV: NMR Relaxation";
Concepts in Magnetic Resonace 6, 137-162, (1994)
Conventions Concerning Solid-state NMR
Robin K. Harris; "Conventions for tensor quantitites used in NMR, NQR and ESR";
Nuclear Magnetic Resonance 10, 177-178, (1998)
Cynthia J. Jameson; "Reply to 'conventions for tensor quantities used in nuclear magnetic resonance, nuclear quadrupole
resonance and electron spin resonance spectroscopy";
Nuclear Magnetic Resonance 11, 265-268, (1998)
BIOMOLECULAR SOLID STATE NMR:
Advances in Structural Methodology and Applications to Peptide and Protein Fibrils. Tycko, R.
Annual Review of Physical Chemistry (2001)
E. R. Andrew, A. Bradbury, and R. G. Eades, Nature 182, 1659 (1958)
I. J. Lowe Physics Rev. Lett. 2, 285, (1959)