Protein folding and intermediates.

With the exception of the discovery of the rate of formation of the earliest intermediates, there have been no major conceptual leaps in our understanding of protein folding reactions over the past two years. Rather, this period has seen an extension of two established techniques: first, mutational analysis combined with a kinetic definition of the energy landscape of the reaction; and second, the use of hydrogen/deuterium exchange of backbone amide groups combined with NMR. Owing to the application of these methods to a wider range of proteins, it is now possible to draw some general conclusions about the physical processes that direct a protein to its native fold.