NMR Studies of Protein Dynamics and Folding
We have become familiar over the last 20 years with the nature of the compact globular states of proteins, initially from studies of protein crystals by diffraction methods (Richardson, 1981) and more recently also from direct structure determination in solution by NMR techniques (Wüthrich, 1989). In addition, from both these experimental techniques, and from theoretical studies, many details of the dynamical properties of these folded states have been revealed (McCammon and Karplus 1983). By contrast, however, very little is known about the unfolded or partially folded states of proteins, primarily because of the intrinsic difficulties inherent in their study. Crystallization of proteins in such states has not been achieved, and indeed seems unlikely to be possible in general. NMR spectroscopy, however, seems ideally suited to their characterization, as it is able to provide both structural and dynamical information about molecules in solution. The methods required for such studies may, however, be very different from those now becoming familiar from studies of proteins in their globular states. Further, the nature of any conformational description may need to be significantly different from that used for the globular state, because of the much greater conformational freedom likely to be characteristic of the unfolded or partially folded states.
KeywordsIntact Protein Amide Proton Protease Domain Folding Pathway Individual Residue
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