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Table 4 Modifications of the reduced Neumann’s model to reproduce the experimental data by Bentele et al

From: Model composition through model reduction: a combined model of CD95 and NF-κB signaling pathways

Step Changed parameters and concentrations Initial values, modifications Reason Ranges and initial values of fitting
1 CD95R:FADD 91.266 nM, increase Case: anti-CD95 = 5 μg/ml Procaspase-8 is cleaved in about 30 minutes. This is possible only if DISC concentration reaches a level sufficient to accelerate the reaction nr2. [102, 103], 442.821, Bentele et al.
2 procaspase-8 64.477 nM, increase Case: anti-CD95 = 5 μg/ml The concentration of caspase-8 should reach its maxim value in about 20 minutes. [102, 103], 442.821, Bentele et al.
3 FLIPS 5.084 nM, increase Case: anti-CD95 = 200 ng/ml As mentioned in Table 2, activation of caspase-8 is mainly caused by caspase-3 and, therefore, is delayed approximately for 30 minutes. Since reactions nr2 and nr5 have the same rates, we cannot observe the delay, but when we reduce the rate of nr5, we can. The latter is achieved by upregulation of the DISC:pro8 complex inhibition. [101, 102], 65.021, Bentele et al.
4 k10 0.121 nM-1min-1, decrease by an order of magnitude Case: anti-CD95 = 200 ng/ml Preventing a rapid growth of caspase-8 concentration. 0.012
5 procaspase-3 1.443 nM, refitting Case: anti-CD95 = 5 μg/ml Improving approximation of the experimental data by Bentele et al. [100, 101], 1.443, Neumann et al.
6 Bid, procaspase-9 5.003 nM, 2.909 nM, replacement by Bentele’s values Case: anti-CD95 = 200 ng/ml Reproducing the experimental dynamics of procaspase-9. 231.760 (Bid), 245.101 (pro-9), Bentele et al.