Make binding to compounds available

[TWendl]

This is of particular interest when modeling PK of proteins and a full blown, free floating target as binding partner is required for proper description of PK, e.g. an antibody binding to a protein, both free floating in plasma, binding to FcRn and endosomally cleared.

[msevestre]

@TWendl Is there any consensus as how this should be implemented?

[PavelBal]

The only way I see it work is to model the binding partner and the complex as "normal" PBPK compounds, perhaps with restriction to plasma and endosomal space. This leads to 3 PBPK models per compound instead of one - but might be necessary.

[TWendl]

Currently, PK-Sim offers binding to "static/stationary" proteins via definition of Kd, Kon, Koff (2 of the 3 parameters). Exactly this feature should be extended to compounds , i.e. full blown protein models, to include their circulation in the blood as well as FcRn binding, etc.

[Yuri05]

Currently, if a compound bounds to a protein My Protein and My Protein is also included into compounds list during simulation creation, we get an error message:

Suggestion would be: just use My Protein (=floating molecule selected in the compound list) as a binding partner.

The question is: how to set initial values of My Protein? Set all = 0 (as for other floating molecules) or set accordingly to Reference Concentration and relative expressions defined in the individual?

[StephanSchaller]

The question is: how to set initial values of My Protein? Set all = 0 (as for other floating molecules) or set accordingly to Reference Concentration and relative expressions defined in the individual?

That is a valid question, but I guess @TWendl is thinking about binding of 2 exogeneous compounds, so you would have initial conditions of C = 0 ... This is also the easier implementation

But I think we should consider the option of endogeneous floting proteins, that can be bound by compounds and maybe define template models for these (and have predefined ICs, turnover rates (i.e. enogeneous production/secretion and clearance).

perhaps with restriction to plasma and endosomal space

I wouldn't restrict this, but maybe offer an option to define ka/kd separately for each compartment type... or if we want to go full blown, have ka/ks for each single compartment (and an interface to change these like for partition coefficients or permeability)

[Yuri05]

I wouldn't restrict this, but maybe offer an option to define ka/kd separately for each compartment type... or if we want to go full blown, have ka/ks for each single compartment (and an interface to change these like for partition coefficients or permeability)

I think this should not be implemented in PK-Sim. At least not in the first iteration. Once the feature is implemented, we can think about it again.