Fig. 3.

A folding funnel. The funnel landscape depicts protein folding as a process that proceeds from a high entropy, disorganized state lacking in intramolecular interactions (mouth), to a low entropy, organized state with native intramolecular interactions (spout). Evolution has selected sequences that avoid frustrating traps en route from mouth to spout, smoothing what might otherwise be a rugged landscape. Under folding conditions, individual molecules can follow any route from mouth to spout, like a ball rolling down a free energy hill. One such trajectory is shown here. For a gallery of variant funnel landscapes, see ref. 126.