Tập tin:BBL.jpg

This is a two-dimensional slice of a three-dimensional energy surface, with the conformations formed at higher temperatures being higher-energy structures. BBL is referred to as a downhill folder because of the very low energy barriers that exist between conformational states. The landscape theory of protein folding implicates numerous paths and thus mechanisms for passing from the unfolded to the folded state. There are many possible unfolded states, and therefore many starting points for folding (of which we are seeing just two), but only one folded state at the bottom of the well. Muñoz and colleagues2 use NMR to provide an unprecedented view of the unfolding of BBL. They reveal that downhill-folding proteins acquire structure gradually, not in an all-or-nothing or highly cooperative process; thus, families of partly cooperative mechanisms must be considered statistically to explain downhill folding.