(* Generated by JWS Online *) (* This is an experimental feature of JWS Online. Please report any mistakes.*) (* Note that the following notable SBML entities or features are not supported in notebook outputyet: *) (* Events *) (* Constraints *) (* Units and UnitDefinitions *) (* AlgebraicRules *) (* conversionFactors *) variables = { ATMA[t], ATMI[t], GADD45[t], IR[t], Mdm2[t], Mdm2\[LetterSpace]P[t], Mdm2\[LetterSpace]mRNA[t], Mdm2\[LetterSpace]p53[t], ROS[t], basalROS[t], damDNA[t], p21[t], p21\[LetterSpace]basal[t], p21\[LetterSpace]mRNA[t], p21step1[t], p21step2[t], p38[t], p38\[LetterSpace]P[t], p53[t], p53\[LetterSpace]P[t], p53\[LetterSpace]mRNA[t] }; initialValues = { ATMA[0] == 0.0, ATMI[0] == 200.0, GADD45[0] == 0.0, IR[0] == 0.0, Mdm2[0] == 5.0, Mdm2\[LetterSpace]P[0] == 0.0, Mdm2\[LetterSpace]mRNA[0] == 10.0, Mdm2\[LetterSpace]p53[0] == 95.0, ROS[0] == 0.0, basalROS[0] == 10.0, damDNA[0] == 0.0, p21[0] == 0.0, p21\[LetterSpace]basal[0] == 7.0, p21\[LetterSpace]mRNA[0] == 1.0, p21step1[0] == 0.0, p21step2[0] == 0.0, p38[0] == 100.0, p38\[LetterSpace]P[0] == 0.0, p53[0] == 5.0, p53\[LetterSpace]P[0] == 0.0, p53\[LetterSpace]mRNA[0] == 10.0 }; rates = { ATMInactivation, ATMactivation, DNAdamage, DNArepair, GADD45activation2, GADD45degradation, Mdm2Degradation, Mdm2Pdegradation, Mdm2Synthesis, Mdm2dephosorylation, Mdm2mRNADegradation, Mdm2mRNASynthesis1, Mdm2mRNASynthesis2, Mdm2phoshorylation, P53\[LetterSpace]Mdm2Binding, P53\[LetterSpace]Mdm2Release, ROSDNAdamage, ROSgenerationP38, ROSremoval, basalROSDNAdamage, p21Synthesis1, p21Synthesis2, p21Synthesis3, p21degradation, p21mRNADegradation, p21mRNASynthesis1, p21mRNASynthesis2, p38activation, p38inactivation, p53Degradation, p53Mdm2IndepDegradation1, p53Mdm2IndepDegradation2, p53Synthesis, p53dephosorylation, p53mRNADegradation, p53mRNASynthesis, p53phoshorylation }; rateEquations = { ATMInactivation -> kinactATM*ATMA[t], ATMactivation -> kactATM*ATMI[t]*damDNA[t], DNAdamage -> kdam*IR[t], DNArepair -> krepair*damDNA[t], GADD45activation2 -> kGADD45*p21[t], GADD45degradation -> kdegGADD45*GADD45[t], Mdm2Degradation -> kdegMdm2*Mdm2[t], Mdm2Pdegradation -> kdegATMMdm2*Mdm2\[LetterSpace]P[t], Mdm2Synthesis -> ksynMdm2*Mdm2\[LetterSpace]mRNA[t], Mdm2dephosorylation -> kdephosMdm2*Mdm2\[LetterSpace]P[t], Mdm2mRNADegradation -> kdegMdm2mRNA*Mdm2\[LetterSpace]mRNA[t], Mdm2mRNASynthesis1 -> ksynMdm2mRNA*p53[t], Mdm2mRNASynthesis2 -> ksynMdm2mRNA*p53\[LetterSpace]P[t], Mdm2phoshorylation -> kphosMdm2*ATMA[t]*Mdm2[t], P53\[LetterSpace]Mdm2Binding -> kbinMdm2p53*Mdm2[t]*p53[t], P53\[LetterSpace]Mdm2Release -> krelMdm2p53*Mdm2\[LetterSpace]p53[t], ROSDNAdamage -> kdamROS*ROS[t], ROSgenerationP38 -> kgenROSp38*kp38ROS*p38\[LetterSpace]P[t], ROSremoval -> kremROS*ROS[t], basalROSDNAdamage -> kdamBasalROS*basalROS[t], p21Synthesis1 -> ksynp21step1*p21\[LetterSpace]mRNA[t], p21Synthesis2 -> ksynp21step2*p21step1[t], p21Synthesis3 -> ksynp21step3*p21step2[t], p21degradation -> kdegp21*p21[t], p21mRNADegradation -> kdegp21mRNA*p21\[LetterSpace]mRNA[t], p21mRNASynthesis1 -> ksynp21mRNAp53*p53[t], p21mRNASynthesis2 -> ksynp21mRNAp53P*p53\[LetterSpace]P[t], p38activation -> kphosp38*GADD45[t]*p38[t], p38inactivation -> kdephosp38*p38\[LetterSpace]P[t], p53Degradation -> kdegp53*Mdm2\[LetterSpace]p53[t], p53Mdm2IndepDegradation1 -> kdegp53mdm2ind*p53\[LetterSpace]P[t], p53Mdm2IndepDegradation2 -> kdegp53mdm2ind*p53[t], p53Synthesis -> ksynp53*p53\[LetterSpace]mRNA[t], p53dephosorylation -> kdephosp53*p53\[LetterSpace]P[t], p53mRNADegradation -> kdegp53mRNA*p53\[LetterSpace]mRNA[t], p53mRNASynthesis -> ksynp53mRNA*Source, p53phoshorylation -> kphosp53*ATMA[t]*p53[t] }; parameters = { kGADD45 -> 4*^-06, kactATM -> 2*^-05, kbinMdm2p53 -> 0.001155, kdam -> 0.007, kdamBasalROS -> 1*^-09, kdamROS -> 1*^-05, kdegATMMdm2 -> 0.0004, kdegGADD45 -> 1*^-05, kdegMdm2 -> 0.000433, kdegMdm2mRNA -> 0.0001, kdegp21 -> 0.00019, kdegp21mRNA -> 2.4*^-05, kdegp53 -> 0.000825, kdegp53mRNA -> 0.0001, kdegp53mdm2ind -> 8.25*^-07, kdephosMdm2 -> 0.5, kdephosp38 -> 0.1, kdephosp53 -> 0.5, kgenROSp38 -> 0.00045, kinactATM -> 0.0005, kp38ROS -> 1.0, kphosMdm2 -> 2.0, kphosp38 -> 0.008, kphosp53 -> 0.006, krelMdm2p53 -> 1.155*^-06, kremROS -> 0.000383, krepair -> 6*^-05, ksynMdm2 -> 0.000495, ksynMdm2mRNA -> 0.0001, ksynp21mRNAp53 -> 6*^-08, ksynp21mRNAp53P -> 6*^-06, ksynp21step1 -> 0.0004, ksynp21step2 -> 4*^-05, ksynp21step3 -> 4*^-05, ksynp53 -> 0.006, ksynp53mRNA -> 0.001, Sink -> 1.0, Source -> 1.0, cell -> 1.0 }; assignments = { }; events = { }; speciesAnnotations = { }; reactionAnnotations = { }; units = { {"time" -> "", "metabolite" -> "", "extent" -> ""} }; (* Time evolution *) odes = { ATMA'[t] == 1.0*ATMactivation +1.0*p53phoshorylation +1.0*Mdm2phoshorylation -1.0*p53phoshorylation -1.0*Mdm2phoshorylation -1.0*ATMInactivation, ATMI'[t] == 1.0*ATMInactivation -1.0*ATMactivation, GADD45'[t] == 1.0*GADD45activation2 +1.0*p38activation -1.0*GADD45degradation -1.0*p38activation, IR'[t] == 1.0*DNAdamage -1.0*DNAdamage, Mdm2'[t] == 1.0*Mdm2Synthesis +1.0*p53Degradation +1.0*P53\[LetterSpace]Mdm2Release +1.0*Mdm2dephosorylation -1.0*Mdm2Degradation -1.0*P53\[LetterSpace]Mdm2Binding -1.0*Mdm2phoshorylation, Mdm2\[LetterSpace]P'[t] == 1.0*Mdm2phoshorylation -1.0*Mdm2dephosorylation -1.0*Mdm2Pdegradation, Mdm2\[LetterSpace]mRNA'[t] == 1.0*Mdm2Synthesis +1.0*Mdm2mRNASynthesis1 +1.0*Mdm2mRNASynthesis2 -1.0*Mdm2Synthesis -1.0*Mdm2mRNADegradation, Mdm2\[LetterSpace]p53'[t] == 1.0*P53\[LetterSpace]Mdm2Binding -1.0*p53Degradation -1.0*P53\[LetterSpace]Mdm2Release, ROS'[t] == 1.0*ROSgenerationP38 +1.0*ROSDNAdamage -1.0*ROSremoval -1.0*ROSDNAdamage, basalROS'[t] == 1.0*basalROSDNAdamage -1.0*basalROSDNAdamage, damDNA'[t] == 1.0*DNAdamage +1.0*ATMactivation +1.0*ROSDNAdamage +1.0*basalROSDNAdamage -1.0*DNArepair -1.0*ATMactivation, p21'[t] == 1.0*p21Synthesis3 +1.0*GADD45activation2 -1.0*p21degradation -1.0*GADD45activation2, p21\[LetterSpace]basal'[t] == 0.0 , p21\[LetterSpace]mRNA'[t] == 1.0*p21mRNASynthesis1 +1.0*p21mRNASynthesis2 +1.0*p21Synthesis1 -1.0*p21mRNADegradation -1.0*p21Synthesis1, p21step1'[t] == 1.0*p21Synthesis1 -1.0*p21Synthesis2, p21step2'[t] == 1.0*p21Synthesis2 -1.0*p21Synthesis3, p38'[t] == 1.0*p38inactivation -1.0*p38activation, p38\[LetterSpace]P'[t] == 1.0*p38activation +1.0*ROSgenerationP38 -1.0*p38inactivation -1.0*ROSgenerationP38, p53'[t] == 1.0*Mdm2mRNASynthesis1 +1.0*p53Synthesis +1.0*P53\[LetterSpace]Mdm2Release +1.0*p53dephosorylation +1.0*p21mRNASynthesis1 -1.0*Mdm2mRNASynthesis1 -1.0*p53Mdm2IndepDegradation2 -1.0*P53\[LetterSpace]Mdm2Binding -1.0*p53phoshorylation -1.0*p21mRNASynthesis1, p53\[LetterSpace]P'[t] == 1.0*Mdm2mRNASynthesis2 +1.0*p53phoshorylation +1.0*p21mRNASynthesis2 -1.0*Mdm2mRNASynthesis2 -1.0*p53Mdm2IndepDegradation1 -1.0*p53dephosorylation -1.0*p21mRNASynthesis2, p53\[LetterSpace]mRNA'[t] == 1.0*p53mRNASynthesis +1.0*p53Synthesis -1.0*p53mRNADegradation -1.0*p53Synthesis }; timeCourse = NDSolve[Join[odes, initialValues]//.rateEquations//.assignments//.parameters, variables, {t, 0, 100}]; (* Steady-state solution initialized with result of time evolution *) findRootEquations = odes /.D[_[t],t]->0; findRootVariables = Partition[Flatten[{#, #/.timeCourse/.t->100} &/@variables],2]; steadyStateVariables = FindRoot[findRootEquations//.rateEquations//.assignments//.parameters, findRootVariables, MaxIterations->100] fluxes = #//.assignments//.parameters/.steadyStateVariables&/@rateEquations (* Plot the time evolution of the variables *) plotTable=Table[Plot[variables[[i]]/.parameters/.timeCourse,{t,0,100},PlotLegends->variables[[i]],PlotRange->Full],{i,Length[variables]}]