TABLE 3.
Experiments to be performed for estimation of dimerization parameters
Parameter No. | Parameter description | Output to be measured | Cell line |
---|---|---|---|
13 | BR for EGFR homodimer dissociation. | HER3 phosphorylation | EGFR/HER3 |
14 | BR for HER2 homodimer dissociation. | HER2 In/Sur ratio | EGFR/HER2 |
15 | BR for EGFR-HER2 dissociation. | EGFR In/Sur ratio | EGFR/HER2 |
16 | BR for HER3 homodimer dissociation. | HER3 phosphorylation | EGFR/HER3 |
17 | BR for HER2-HER3 dissociation. | HER3 phosphorylation | EGFR/HER2/HER3 |
18 | BR for EGFR-HER3 dissociation. | HER3 phosphorylation | EGFR/HER3 |
19 | Dissociation rate enhancement upon dephosphorylation. | HER2 In/Sur ratio | EGFR/HER2 |
20 | Dissociation rate enhancement upon ligand removal. | HER3 phosphorylation | EGFR/HER3 |
50 | Enhanced incorporation factor for ligand-bound EGFR. | EGFR In/Sur ratio | EGFR |
51 | Enhanced incorporation factor for ligand-bound EGFR-HER2. | HER2 In/Sur ratio | EGFR/HER2 |
52 | Enhanced incorporation factor for ligand-bound EGFR-HER3. | HER3 In/Sur ratio | EGFR/HER3 |
BR stands for the basal rate. The relative RMSD between experimental observables generated using the base parameter set and a parameter set with a 10% change in a single model parameter was computed for all the dimerization parameters for four possible HER-expressing cell lines. These RMSD values were used to determine the experimental output that would serve to provide the best data set for estimation of each of the parameters listed. Experiments that turn out to be the best ones for the estimation of multiple parameters are italicized.