Figure 1.

A schematic view, according to the capillarity picture of structure of a protein (lysozyme is shown for illustration) once it is advanced partially down the folding funnel. When several phases of the protein are possible, they can lead to a rather complex interface, as illustrated here. Thermal- and disorder-induced roughening of the interfaces can smooth out the transition region seriously. The figure shows several kinds of ordering that are possible: a region in which side chains are completely ordered (blue), a transition zone with topologically correct folding but no side-chain order (red), a molten-disordered phase (yellow), and the random coil (green). Having such a gradual progression of phases can lower the activation energy but broadens the interface between completely folded and unfolded regions. The front is shown, for clarity, as progressing from one end of the protein to the other. The most well ordered part may be buried in the core, depending on the relative surface tensions between the phases and the solvent.