A long-term plan for the LS model

[aarmey]

Ultimately, the value of the LS model is to identify when Gas6 and PROS1 operate differently, either alone or when present in combination. If we identify cases where these behaviors take place, they can be experimentally verified, and support our model for how the TAM receptors function.

To identify these cases, I think these tasks may help:

• For a constant concentration of ligand, make a plot that sweeps from 100% Gas6 to 100% PROS1. If there's a linear relationship between these extremes it's not all that interesting, but there might be cases where the combination is unique. PROS1 has a very different affinity, so it might have to be a sweep between concentrations that are adjusted to give the same pY.
• Plotting the dose response behavior of each ligand at 1 min, 30 min, 4 hrs.
• Plotting the concentration of G/P containing dimers vs. G/G and P/P dimers in the first plot. If the ligands have very different behavior when present in combination, my guess is that would come from receptor dimers composed of both ligands.

Some challenges we'll need to address:

• Parameter values. We have a good idea of many of these, but might need to fit to available data to make sure they are correct. The biggest challenge will be PROS1 binding—those affinities are very weak, so we don't have estimates of them.
• Presenting/describing the model. With two ligands, there's a combinatorial issue that arises, such that the model is much more complex compared to the one-ligand case. We'll need to write out the model for a methods section, and make a graphic that concisely describes all the interactions. We can borrow from Meyer et al, Cell Systems.
• We may have to account for the effect of PS, which would mean making a compartmental form of this model.

[aarmey]

@ajtsao1 which of these have we created? You can check the checkbox for those we have.