Nuclear magnetic resonance spectroscopy (usually abbreviated to NMR) applied to the field of structural biology uses NMR spectroscopy to obtain information about the structure and dynamics of proteins, nucleic acids, and their complexes. The field was pioneered by, among others, Kurt Wüthrich, who shared the Nobel Prize in Chemistry in 2002. NMR techniques are continually being used and improved in both academia and the biotech/pharmaceutical industry. Structure determination by NMR spectroscopy usually consists of several phases, each using a separate set of highly specialized techniques. The sample is prepared, measurements are made, interpretive approaches are applied, and a structure is calculated and validated.

NMR involves the quantum mechanical properties of the central core ("nucleus") of the atom. These properties depend on the local molecular environment, and their measurement provides a map of how the atoms are linked chemically, how close they are in space, and how rapidly they move with respect to each other. These properties are fundamentally the same as those used in the more familiar Magnetic Resonance Imaging (MRI), but the molecular applications use a somewhat different approach, appropriate to the change of scale from millimeters (of interest to radiologists) to nanometers (bonded atoms are typically a fraction of a nanometer apart), a factor of a million. This change of scale requires much higher sensitivity of detection and stability for long term measurement. In contrast to MRI, structural biology studies do not directly generate an image, but rely on complex computer calculations to generate three dimensional molecular models.

A typical study might involve how two proteins interact with other, possibly with a view to developing small molecules which can be used to probe the normal biology of the interaction ("chemical biology") or to provide possible leads for pharmaceutical use ("drug development"). Frequently, the interacting pair of proteins may have been identified by studies of human genetics, indicating the interaction can be disrupted by unfavorable mutations, or they may play a key role in the normal biology of a "model" organism like the fruit fly, yeast, the worm C. elegans, or mice.

To prepare a sample, methods of molecular biology are typically used to make quantities by bacterial fermentation. This also permits changing the isotopic composition of the molecule, which is desirable because the isotopes behave differently and provide methods for identifying overlapping NMR signals. Currently most samples are examined in a solution in water, but methods are being developed to also work with solid samples. Data collection relies on placing the sample inside a very powerful magnet, and sending it radio frequency signals to subsequently receive radio frequencies from the sample which tell us the NMR properties. Many atoms will produce separate radio frequencies, and the jigsaw puzzle of using the data is to connect the signal frequencies which are from atoms bonded together and from those which are close in space (typically less than 0.5 nanometers). Various tricks of timing and sending specific radio frequency signals into the sample are used for this purpose.

The scientist then solves the "jigsaw puzzle" using computer programs to make sense of all the signals. Scientists are still improving these methods and making a lot of effort to push them into understanding the molecular motions fully. NMR has a big advantage in that it is sensitive to molecular motions needed for recognition between molecules, and for chemical changes by catalysis.

Because it looks at a very low energy interaction, NMR is intrinsically hard to do, and that's why the instruments are large and expensive.

Related information

http://en.wikipedia.org/wiki/Nuclear_magnetic_resonance
http://www.cem.msu.edu/~reusch/VirtualText/Spectrpy/nmr/nmr1.htm
http://nmrwiki.org/wiki/index.php?title=Main_Page