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Pathway Modeling of the MAPK cascade. Rishi Khan, Wenzhong Wang, Nate Woody. Goals. Model the MAPK Cascade pathway using Virtual Cell Create accesible geometry Input kinetic parameters Validate the Model Examine overall behavior of model Examine models sensitivity to key parameter changes
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Pathway Modeling of the MAPK cascade Rishi Khan, Wenzhong Wang, Nate Woody
Goals • Model the MAPK Cascade pathway using Virtual Cell • Create accesible geometry • Input kinetic parameters • Validate the Model • Examine overall behavior of model • Examine models sensitivity to key parameter changes • Experiment • Change number of cascades • Examine unique parameter situations
v1 v2 v3 v4 v5 MAPKK MAPKKK MAPK MAPKKK-P MAPKK-P MAPK-P v6 Modeling the Pathway • MAPK cascade using 6 species • 3 primary reactions Membrane Cytosol
Initial results Kholodenko BN Eur J Biochem 2000 Mar;267(6):1583-8
Parameter importance • Adjusting various parameters by 100x • Notice the strong effect of K3 on M2KP
Adjusting K3 and K4 • Systematic adjustment of K3 and K4 • All other parameters remain the same • High values approach linearity
Effects of Cascading • First order response of first cascade • Second order response of second cascade • MAPKP increases and decreases faster than MAPKKP
Advantages No programming False color plots Only public resource Disadvantages Data VERY hard to export Very little control over data display Non-robust (math and interface) Crashes often Evaluation of Virtual Cell