Notes

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  • Two types of simulation is being run. In one type of simulation for Control and for all types of silencing new parameter distribution is generated each time. In the next type of simulation first a parameter distribution is created and with that same parameter distribution the ensemble models of control and PYK silencing is being generated.
  • When we silence the model using our sekeleton model, the PEP accumulates and PYR depletes. But when we considered the parameter distribution for other parameters it behaves differently.
  • When we silence the Pyruvate Kinase (dividing Vmax of PYK with 2 or 4) the PEP is supposed to accumulate and PYR is supposed to deplete. In our model PYR does deplete but PEP does not accumulate. The rate laws has been verified and no mistake was found there. Therefore now the impact of other parameters on this silencing activity is being adjusted.
  • We tried to first find out which factor is the most appropriate to divide the Vmax. We found that till factor 4 the PEP accumulates and after factor 4 although PEP concentration is higher than control but it is lower than the conecntration we get by dividing with 4.
  • We then generated 225 stead-states from control model using 300 total parameters. We used this 225 SS models to simulate steady-state for Pyruvate Kinase silenced by dividing Vmax with 4. This gives 202 SS models in PYK_Silence. We then deleted the No-steady state models of PYK_Silence from Control Data.
  • We then wrote a Matlab script to filter the steady-state restul from both Control and PYK_Silence for which the PEP concentration is higher in PYK_Silence compared to Control. We did this because we wanted to associate this fundamental inforamtion with our model and this is one of the criteria that the models should satisfy in order to perform correctly. This gives a total of 108 models where PEP is accumulated and Pyr is consumed in PYK_silence compared to Control
  • We then took the parameter distirubtion associated with this 108 models to simulate the steady-state for different extracellular Serine conecentration.