Figure 1.

Possible mechanisms for the (de)stabilization of the native state by ligands. The ligand binding to different states results in different thermodynamic effects on proteins. (A) The ligand preferentially binds to the native state (N), which results in the stabilization of the native state (ΔΔG < 0). (B) The ligand preferentially binds to an intermediate state (I) or the denatured state (D), which results in the destabilization of the native state (ΔΔG > 0). Note that ΔΔG=ΔG _free − ΔG _ligand.