Mathematical modeling of the microtubule detyrosination/tyrosination cycle for cell-based drug screening design
Fig 5
Prediction of drug combinations for potential new screen for neurodegenerative disorders.
(A) Perturbed numerical simulation in the model CDTN. The detyrosinated microtubule depolymerization rate constant km1 is increased by a factor ten at 60 units of time (min). The numerical simulation shows a slight increase of tyrosinated species suggesting that when the system reached its steady state, increasing the detyrosinated microtubule depolymerization reaction alone does not enable an increase of the tyrosination status. (B) Perturbed numerical simulation in the model CDTN. The detyrosinated microtubule depolymerization rate constant km1 and the tyrosination rate constant Vm2 are increased at 60 units of time (min) by a factor ten. The numerical simulation shows that the level of tyrosinated species become quickly larger than detyrosinated species. Increasing in synergy the tyrosination and detyrosinated microtubule depolymerization reactions is predicted to be sufficient to trigger a significant increase of the tyrosinated species. (C) Prediction of drug combinations combining an increase of the tyrosination rate constant (Vm2) and the detyrosinated microtubule depolymerization rate constant (km1) by different factors showing a synergistic effect to increase the tyrosination status. (D) Perturbed numerical simulation in the model CDTN. The detyrosination rate constant k1 is decreased by a factor one hundred at 60 units of time (min). The numerical simulation shows that tyrosinated species slowly increase and become predominant at steady state.