Mapping Protein Folding Landscapes by NMR Relaxation

Abstract

The process of protein folding provides an excellent example of the interactions of water with biomolecules. The changes in the water–protein interactions along the protein folding pathway provide an important impetus for the formation of the final natively folded structure of the protein. NMR spectroscopy provides unique insights into the dynamic protein folding process, and during the past 20 years we have seen the development of a wide range of NMR techniques to probe the kinetic and thermodynamic aspects of protein folding. In particular, with the advent of high-field spectrometers and stable isotope labeling techniques, the structure and dynamics of a wide range of disordered and partly ordered proteins at equilibrium have been characterized by NMR. Efforts in our laboratory over a number of years have allowed the sequence-specific identification of sites of local hydrophobic collapse, as well as secondary structure formation and transient long-range interactions in several protein systems, most notably for apomyoglobin, which will be highlighted in this article.