LOCK AND KEY

Binding is reversible

A transmitter binds its receptor and lets go again, many times a second. At any moment some fraction of the receptors are occupied, and that fraction depends on how much transmitter is around and how tightly it binds.

More ligand means more occupied receptors, up to a limit.

THE CURVE

Occupancy against concentration

The curve rises, then flattens as receptors fill up. A weaker binder needs more ligand for the same occupancy.

Tighter binders reach 50% at lower concentrations.

THE FORMULA

Occupancy from Kd

Occupancy = [L] ÷ ([L] + K_d)

[L] is the free ligand concentration, and K_d is the dissociation constant, the concentration at which half the receptors are occupied. A smaller K_d means tighter binding, or higher affinity.

Kd is the concentration for half occupancy.

A WORKED EXAMPLE

A ligand with K_d = 10 nM

At 1 nM 1 ÷ (1 + 10) ≈ 9% occupied

At 10 nM 10 ÷ (10 + 10) = 50% occupied

At 100 nM 100 ÷ (100 + 10) ≈ 91% occupied

A tenfold change in concentration moves occupancy from about 9% to about 91%.

BINDING VS ACTING

Affinity is not the same as effect

🟢

Agonist

Binds and activates the receptor

🔴

Antagonist

Binds and blocks activation, without activating it

🟡

Partial agonist

Binds and activates only weakly

Affinity is how tightly it binds. Efficacy is what it does once bound.

UNIT 11 STUDY COMPLETE

🔑

Ready for the Fab Challenge?

You've worked out receptor occupancy from Kd and a concentration.