Comparison of equilibrium and kinetic approaches for determining protein folding mechanisms

This chapter presents both the general and specific results obtained from the studies of equilibrium folding intermediates and their relationship to the kinetic pathway of protein folding, suggesting that such equilibrium studies can yield important and insightful information about where in conformational space a protein chain can go and how it gets there.

Abstract

This chapter presents both the general and specific results obtained from the studies of equilibrium folding intermediates and their relationship to the kinetic pathway of protein folding. A detailed comparison between various equilibrium ensembles and kinetic intermediates suggests that such equilibrium studies can yield important and insightful information about where in conformational space a protein chain can go and how it gets there. As with many properties of proteins, the relationship between the partially folded ensembles populated at equilibrium and those transiently populated during the folding reaction depends on the particular protein in question. Because they sample different regions of the energy landscape, kinetic and equilibrium intermediates will not necessarily be similar. For most proteins, however, there appears to be a dominant region that is the first to fold and/or the most stable. In other proteins, this trend is less clear, with only a subset of the interactions of equilibrium intermediates seen in kinetic intermediates. As more results and techniques become available, it helps to learn more about why a particular region of a protein may have a stronger influence on its folding and stability.