Ligand-receptor interactions

The study of pharmacodynamics is based on the concept of ligand-receptor interactions. Remember Ehrlich’s principle: "a drug will not act, unless bound"

When a ligand or drug binds to its receptor, a response may result. The simplest interaction of receptor and ligand is described by the equation:

L + R LR

  • L = free ligand (sometimes, letter 'A' (for agonist/antagonist) is used)
  • R = free receptor
  • LR = bound ligand-receptor complex
  • K+1= association rate constant (kon)
  • K-1 = dissociation rate constant (koff)

Note that K+1 and K-1 are also called Kon and Koff, and are intrinsic properties of any given ligand-receptor pair.

Binding affinity is usually measured and defined by the equilibrium dissociation constant, Kd (with the units of Kd usually in nM):

Kd = [L][R] / [LR]     or     Kd = K-1 / K+1

The equilibrium binding constant (Ka) is much less used, and is simply the reciprocal of the Kd:

Ka = 1 / Kd     or     Ka = K+1 / K-1

In literature, it is sometimes confusing what is exactly meant with 'binding equilibrium'. Therefore 'equilibrium dissociation constant', Kd, is generally used and its definition is unquestionable. In practice: The smaller the Kd, the higher the affinity – thus: the more tightly the ligand is bound to the receptor. The opposites is also true:

  • the higher the Kd, the lower the affinity
  • the higher the Ka, the higher the affinity
  • the lower the Ka, the lower the affinity