Ligand Binding: Dissociation Constants and Receptor Occupancy
Binding of a ligand to a receptor reaches an equilibrium set by the dissociation constant, and the fraction of receptors occupied follows a saturating curve. A smaller dissociation constant means tighter binding, so half occupancy is reached at a lower concentration.
What a learner can do afterwards
- Calculates fractional occupancy from a ligand concentration and a dissociation constant.
- Reads a binding curve to get the dissociation constant, and compares two ligands from their curves.
- Explains why raising the concentration far above the constant gains almost nothing.
1 · Read
A ligand grips its receptor, and the strength of that grip is one number: the dissociation constant, Kd. Kd is the ligand concentration at which half the receptors are filled, and the filled fraction follows filled = ligand divided by Kd plus ligand. A smaller Kd means tighter binding, since half occupancy arrives at a lower concentration. This rule assumes one ligand meets one free site in a single step, with plenty of ligand so binding barely changes its level, and each site acts alone.
Take a ligand with Kd 10 nanomolar. At 10 nanomolar it fills half the receptors. At 90 nanomolar it fills about 90 percent, since 90 divided by 100 is 0.9. Near 1000 nanomolar it fills about 99 percent.
Plot filled fraction against concentration and the curve climbs steeply, then flattens toward full. Read Kd off it: the concentration on the horizontal axis where the curve passes half full. Put two ligands on shared axes and the tighter binder is the curve rising earlier, reaching half full at the lower concentration, which is the smaller Kd.
Raising the concentration far above Kd gains almost nothing, because the curve is nearly flat up there. Moving from 10 times Kd to 20 times Kd shifts occupancy only from about 0.91 to 0.95. Save ligand: once nearly all receptors are filled, more buys nearly nothing.
Kd marks half full, the curve reads off Kd, and excess ligand past Kd buys almost nothing.
The rewritten readings were written for this dataset.
2 · Watch
Take it off screen
Where it sits
Where this leads
Jobs that lean on this skill. Follow one to see everything it is built on.
8 questions wait behind this lesson, each with its answer explained. Every answer feeds the sky: stars light as they are learned, and dim when it is time to come back.