Figure 4.35 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 may 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.