Protein unfolding mechanisms and their effects on folding experiments

In this review, I discuss the various methods researchers use to unfold proteins in the lab in order to understand protein folding both in vitro and in vivo. The four main techniques, chemical-, heat-, pressure- and force-denaturation, produce distinctly different unfolded conformational ensembles. Recent measurements have revealed different folding kinetics from different unfolding mechanisms. Thus, comparing these distinct unfolded ensembles sheds light on the underlying free energy landscape of folding.