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Binding Reactions

Soluble—soluble binding

This reaction type involves the binding of two soluble proteins (or protein complexes). It is described as a bimolecular binding step and unimolecular dissociation step. The complex formed in this reaction is also soluble. The fundamental rate constants are lumped together into an equilibrium dissociation constant (Kd). By default, these will be the same values in all model compartments, but the Kds of drug–target binding can be modeled as different in different compartments to describe some more sophisticated mechanisms such as pH dependent binding. To model this, use the Drug:Target Kd scale parameters, which are multiplicative scaling factors on the Drug:Target KD parameter in its respective compartment.

Reaction schema

\( \ce{ Sol_1 + Sol_2 <->[k_{on}][k_{off}] Sol_3 } \)


Relate elementary rate constants to equilibrium binding constants

\[ K_{D} = \frac{k_{off}}{k_{on}} \]
\[ k_{on} = 1e-3 nM^{-1} s^{-1} \]

Soluble — membrane binding

This reaction type involves the binding of one soluble protein (or protein complex) to one membrane complex. It is the same as the Soluble—Soluble reaction type except that one reactant is membrane protein and the product is membrane. Note that even though one of the states in the bimolecular reaction is not soluble, the same on-rate is used. This reflects the fact that the default on-rate is significantly slower than the hard sphere due to other factors dominating the on-rate. As such, the reduced diffusivity of one of the reactants (due to being cell bound) does not typically show up as a different on-rate.

Bivalent soluble — membrane binding

A common combination, particularly for antibodies, is soluble binding followed by membrane binding. Here we are assuming random order symmetric binding for the first step and then symmetric binding for the second step.

Reaction schema

\( \ce{ Sol_1 + Mem <->[k_{on}][k_{off}] Sol1:Mem } \)
\( \ce{ Sol_1:Mem + Mem <->[k_{on,2d}][k_{off,2d}] Sol1:Mem:Mem } \)