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a workhorse can't do everything. The dual advantages of high resolution
and fast throughput make synchrotron-based x-ray crystallography,
like that which is being carried out at Berkeley Lab's Advanced Light
Source, the undisputed mainstay for solving protein structures. However,
some 20 to 40 percent of all proteins are extremely difficult or even
impossible to crystallize, including many found in the membranes which
control the transportation of molecules and communication of signals
across cell surfaces. This means that other technologies will also
have critical roles to play.
One alternative that does not require crystallized proteins is nuclear
magnetic resonance (nmr) spectroscopy, a technology that exploits
the spin of certain atomic nuclei to obtain structural, spatial, and
even dynamic information about those nuclei. Conventional nmr spectroscopy,
however, is essentially limited to the study of small proteins. For
the study of macromolecular protein complexes, especially those that
are difficult to coax into crystals, the best alternative to x-ray
crystallography may be electron microscopy.
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