Structural Biology at NIH - NMR spectroscopy
NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY
During the past decade, tremendous advances in both NMR and
computational methodologies have taken place. These advances now
permit the determination of three-dimensional solution structures of
proteins up to 20 to 30 kDa by NMR that are comparable to
high-resolution crystal structures. Work is continuing to push this
size limit up to 40 kDa, and it is clear that limited structural
information, based on a specific site or structural feature, is
available for proteins up to 50 kDa. These developments are extremely
powerful and open up the possibility to investigate structural and
dynamic properties of systems that may not be amenable to
crystallography. The NMR approach is complementary to
crystallography, and often one methodology can guide the other in
structure refinement or in addressing some specific structural problem,
such as the effects of site-specific mutagenesis. In addition to
examination of systems that do not crystallize, NMR can reveal dynamic
information about regions of macromolecular structure and conformation
or structural changes that occur as a result of ligand binding. The
investigation of solution properties and functions of native proteins
or nucleic acids and the action of drugs developed against these
systems may be examined in detail. Some excellent examples are
referenced in the following profiles.
The NIH is recognized world-wide as a leader in many of these
developments and is enriched by a broad range of research groups
participating in this field. The groups are complementary to one
another and often share ideas and technology. There is also support
and collaboration among other segments of the overall structural
biology effort at NIH. Among these elements are the necessary
molecular biology and protein expression required to pursue this type
of research. This situation makes for a very vibrant and invigorating
environment in which to pursue research interests that range from the
development of new methodology to the structural elucidation of
proteins, nucleic acids, and carbohydrates.