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Ligand-Receptor Affinity

Ligand-Receptor Affinity, \(K_{D,L:R}\), is the equilibrium dissociation constant for a soluble ligand and its receptor. It is a measure of the strength of binding between two proteins. For multivalent ligands, this parameter is the monovalent affinity of the molecule.

The role of \(K_{D}\) in determining the on and off rates of binding is discussed in the binding section of model mechanisms.

Ligand-Receptor Affinity in Assess

Ligand-receptor affinity can often be found directly in literature. Common assays for measuring affinity include surface plasmon resonance (SPR), competition binding assays, and scatchard analysis. These assays are often performed with recombinant protein, which can impact interpretation of these values. In the absence of direct binding affinity measurements, the EC50 of activity assays can be used as a surrogate.

If one of the binding partners is unknown or excluded from the model, large values (>1000 nM) can be used to eliminate binding within the model.

Example: Binding of Activin A to its receptor ACVR2/ActIIRb

The figure below reproduces a radiolabeled competition binding assay. The \(K_{D}\) is the concentration of ligand resulting in a reduction of CPM by half of the maximum, or about 400 pM.

Activin A radiolabeled competition binding assay
Image licensed under CC-BY 4.0. (Harrsion et. al. 2004)

This measurement is consistent with other sources for Activin A binding affinity (Donaldson et. al. 1992, Matthews et. al. 1991)

When a range of values exists in literature, scanning over the reported range can identify potential impacts on model behavior.