Equilibrium dissociation constant

The equilibrium dissociation constant, or K_D, refers to the concentration of a ligand that occupies 50% of an available population of receptors in the absence of any other competing ligand. The K_D can be obtained from a binding curve for the interaction of the ligand with the receptor of interest. The higher the binding affinity, the lower the K_D value. An in-depth discussion of the parameters contributing to the value for K_D may be found under the entry for affinity.

A ligand will have different K_D values for different proteins, with the lowest K_D usually being for its “target” protein. As a result, low concentrations or doses of a drug will show selectivity for binding to its target protein, but if concentrations of free drug in the body increase (perhaps as a result of increasing the dose, or competition for plasma protein binding, or reducing clearance by inhibiting CYP enzymes) then the drug can start to bind to a significant proportion of one or more alternative proteins, as well as to a greater proportion of the target proteins. This may result in both on and off target side effects.