text: Most NMR studies of protein structure are based on analysis of the Nuclear Overhauser effect, NOE, between different protons in the protein. Because the NOE depends on the inverted sixth power of the distance between the nuclei, r, NOEs can be converted into distance restraints that can be used in molecular dynamics-type structure calculations. RDCs provide orientational restraints rather than distance restraints, and has several advantages over NOEs:
  *RDCs give information about the angle relative to the external magnetic field, which means that it can give information about the relative orientation of parts of the molecule that are far apart in the structure.
  *In large molecules (>25kDa) it is often difficult to record NOEs due to spin diffusion. This is not a problem with RDCs.
  *Analysis of a high number of NOEs can be very time consuming.
  Provided that a very complete set of RDCs is available, it has been demonstrated for several model systems that molecular structures can be calculated exclusively based on these anisotropic interactions, without recourse to NOE restraints. However, in practice, this is not achievable and RDC is used mainly to refine a structure determined by NOE data and J-coupling. One problem with using dipolar couplings in structure determination is that a dipolar coupling does not uniquely describe an internuclear vector orientation. Moreover, if a very small set of dipolar couplings are available, the refinement may lead to a structure worse than the original one. For a protein with N aminoacids, 2N RDC constraint for backbone is the minimum needed for an accurate refinement.
  The information content of an individual RDC measurement for a specific bond vector (such as a specific backbone NH bond in a protein molecule) can be understood by showing the target curve that traces out directions of perfect agreement between the observed RDC value and the value calculated from the model.  Such a curve (see figure) has two symmetrical branches that lie on a sphere with its polar axis along the magnetic field direction. Their height from the sphere's equator depends on the magnitude of the RDC value and their shape depends on the "rhombicity" (asymmetry) of the molecular alignment tensor.  If the molecular alignment were completely symmetrical around the magnetic field direction, the target curve would just consist of two circles at the same angle from the poles as the angle  that the specific bond vector makes to the applied magnetic field.
  In the case of elongated molecules such as RNA, where local torsional information and short distances are not enough to constrain the structures, RDC measurements can provide information about the orientations of specific chemical bonds throughout a nucleic acid with respect to a single coordinate frame. Particularly, RNA molecules are proton-poor and overlap of ribose resonances make it very difficult to use J-coupling and NOE data to determine the structure. Moreover, RDCs between nuclei with a distance larger than 5-6 Å can be detected. This distance is too much for generation of NOE signal. This is because RDC is proportional to r whereas NOE is proportional to r.
  RDC measurements have also been proved to be extremely useful for a rapid determination of the relative orientations of units of known structures in proteins. In principle, the orientation of a structural subunit, which may be as small as a turn of a helix or as large as an entire domain, can be established from as few as five RDCs per subunit.