NMR studies of protein folding

NMR spectroscopy is the method of choice for determining the structural details of unfolded and partially folded states of proteins. Here, the utility of NMR spectroscopy in characterizing such disordered states which populate protein folding pathways, is discussed. The relevance of the structural information obtained to protein folding mechanisms is examined critically. NMR spectroscopy can not only be applied directly for characterizing disordered states of proteins populated at equilibrium, but can also be applied indirectly, in concert with hydrogen exchange, for characterizing equilibrium as well as kinetic intermediate states of proteins. Structural and dynamic characterization by NMR spectroscopy of protein conformations in the unfolded and intermediate state ensembles are important for elucidating the early events in protein folding, and for determining how folding is channelled along specific routes to attain the unique three-dimensional native protein structure.