(a) An example of a free energy diagram often used to
describe protein folding and unfolding. The free energy,
G, is plotted as a function of a generalized folding
coordinate, x. The symbols U, ‡, and
F represent the unfolded ensemble, the transition state
ensemble, and the folded ensemble, respectively. (b)
An example of how an imperfect compensation of entropy (TS)
and enthalpy (H) leads to a (in this case, entropic) barrier on the
folding coordinate. (c) A two-dimensional free
energy diagram allowing for multiple unfolding pathways.
x1 and x2
represent generalized unfolding reaction coordinates.