Fig. 1.

Illustration of the analogy between the free-energy landscapes for liquid and protein-conformational dynamics. (A) The log-number of states (i.e., entropy), as a function of energy, for two systems with similar free-energy landscapes. At liquid-to-crystal transition, the system increases its entropy by phase separation and follows the red line, while bypassing the structural states intermediate between the liquid and crystal states. Analogously, to fold, the protein must bypass glassy, trap states that are intermediate between the numerous, highly mobile molten globule states, and the native states. (B) A funnel-like landscape that reflects a scarcity of configurations between a set of numerous high-energy states, where transport is facile, and a unique low-energy, stable structure. It is essentially the entropy plot from A turned on its side.