Figure 1.

At the bottom of a folding funnel (shown enclosed by a small circle, which is projected and magnified in the larger circle), there are many distinctive, accessible conformations around the most populated native structure. For clarity, only the native structure and the functional conformation are highlighted in the figure. They are indicated by the schematic drawings as N_a and F_a, respectively. The conformational change responsible for the cascade reaction in binding is drawn opposite to the binding site to reflect that it is remote from the binding site. On binding (indicated by a dashed rectangle), the environment changes. The change in the environment has the effect of making the folding energy surface shift, to favor the functional conformation (F_b) instead of the native structure (N_b). Hence, in terms of the free energy landscape theory, the functional switch-on mechanism is not by induced and propagated conformational change of the protein molecule through binding; rather, it is a shift of the population toward the functional conformer.