Folding funnel. The folding funnel depicts the thermodynamics of protein folding. The top of the funnel represents all possible denatured conformations—that is, maximal conformational entropy. Depressions on the sides of the funnel represent semistable intermediates that can facilitate or hinder the formation of the native structure, depending on their depth. Secondary structures, such as helices, form and collapse onto one another to initiate folding.

[After D. L. Nelson and M. M. Cox, Lehninger Principles of Biochemistry, 5th ed. (W. H. Freeman and Company, 2008), p. 143.]