WHAT IS EFFICACY

FIGURE 1.9 Time course for increasing concentrations of a ligancl with a Ka of 2 nM. Initially the binding is rapid but slows as the sites become occupied. The maximal binding increases with increasing concentrations as does the rate of binding. 

Thermodynamically it would be expected that a ligand may not have identical affinity for both receptor conformations. This was an assumption in early formulations of conformational selection. For example, differential affinity for protein conformations was proposed for oxygen binding to hemoglobin [17] and for choline derivatives and nicotinic receptors [18]. Furthermore, assume that these conformations exist in an equilibrium defined by an allosteric constant L (defined as [Ra]/[R-i]) and that a ligand [A] has affinity for both conformations defined by equilibrium association constants Ka and aKa, respectively, for the inactive and active states  

It can be shown that the ratio of the active species Ra in the presence of a saturating concentration (p ) of the ligand versus in the absence of the ligand (pg) is given by (see Section 1.13)  

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