Figure 3.

Present two-state model: schematics (A) and a possible simplified illustration (B). A single binding affinity (K _d) is assumed that represents an ensemble average of the binding to the active and inactive conformations. In most cases, direct binding of small-molecule ligand to the active R* form is unlikely (as indicated by the red X mark) since the ligand-binding domain (LBD) sites are buried deep inside the receptor and are not directly accessible from the surrounding environment. Again, the case corresponding to the minimal two-state theory (no constitutive activity, i.e., ligand-free receptor has no active form) is highlighted with a light blue background.