(* 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 = { C1[t], C2[t], C3[t], C4[t], C5[t], C6[t], C7[t], C8[t], C9[t], MAPK[t], MAPKMEKpp[t], MAPKPH[t], MAPKp[t], MAPKpMAPKPH[t], MAPKpMEKpp[t], MAPKpp[t], MAPKppMAPKPH[t], MEK[t], MEKPH[t], MEKRAFp[t], MEKp[t], MEKpMEKPH[t], MEKpRAFp[t], MEKpp[t], MEKppMEKPH[t], RAF[t], RAFK[t], RAFPH[t], RAFRAFK[t], RAFp[t], RAFpRAFPH[t] }; initialValues = { C1[0] == 0, C2[0] == 0, C3[0] == 0.0, C4[0] == 0, C5[0] == 0.0, C6[0] == 0, C7[0] == 0.0, C8[0] == 0.0, C9[0] == 0.0, MAPK[0] == 0.4, MAPKMEKpp[0] == 0.0, MAPKPH[0] == 0.3, MAPKp[0] == 0.0, MAPKpMAPKPH[0] == 0.0, MAPKpMEKpp[0] == 0.0, MAPKpp[0] == 0.0, MAPKppMAPKPH[0] == 0.0, MEK[0] == 0.2, MEKPH[0] == 0.2, MEKRAFp[0] == 0.0, MEKp[0] == 0.0, MEKpMEKPH[0] == 0.0, MEKpRAFp[0] == 0.0, MEKpp[0] == 0.0, MEKppMEKPH[0] == 0.0, RAF[0] == 0.3, RAFK[0] == 0.2, RAFPH[0] == 0.3, RAFRAFK[0] == 0.0, RAFp[0] == 0.0, RAFpRAFPH[0] == 0.0 }; rates = { Reaction1, Reaction10, Reaction11, Reaction12, Reaction13, Reaction14, Reaction15, Reaction16, Reaction17, Reaction18, Reaction19, Reaction2, Reaction20, Reaction21, Reaction22, Reaction23, Reaction24, Reaction25, Reaction26, Reaction27, Reaction28, Reaction29, Reaction3, Reaction30, Reaction4, Reaction5, Reaction6, Reaction7, Reaction8, Reaction9, v\[LetterSpace]ENZ\[LetterSpace]C1\[LetterSpace]NEG, v\[LetterSpace]ENZ\[LetterSpace]C1\[LetterSpace]POS, v\[LetterSpace]ENZ\[LetterSpace]C2\[LetterSpace]NEG, v\[LetterSpace]ENZ\[LetterSpace]C2\[LetterSpace]POS, v\[LetterSpace]ENZ\[LetterSpace]C3\[LetterSpace]NEG, v\[LetterSpace]ENZ\[LetterSpace]C3\[LetterSpace]POS, v\[LetterSpace]ENZ\[LetterSpace]C4\[LetterSpace]NEG, v\[LetterSpace]ENZ\[LetterSpace]C4\[LetterSpace]POS, v\[LetterSpace]ENZ\[LetterSpace]C5\[LetterSpace]NEG, v\[LetterSpace]ENZ\[LetterSpace]C5\[LetterSpace]POS, v\[LetterSpace]ENZ\[LetterSpace]C6\[LetterSpace]NEG, v\[LetterSpace]ENZ\[LetterSpace]C6\[LetterSpace]POS, v\[LetterSpace]ENZ\[LetterSpace]C7\[LetterSpace]NEG, v\[LetterSpace]ENZ\[LetterSpace]C7\[LetterSpace]POS, v\[LetterSpace]ENZ\[LetterSpace]C8\[LetterSpace]NEG, v\[LetterSpace]ENZ\[LetterSpace]C8\[LetterSpace]POS, v\[LetterSpace]ENZ\[LetterSpace]C9\[LetterSpace]NEG, v\[LetterSpace]ENZ\[LetterSpace]C9\[LetterSpace]POS, v\[LetterSpace]ENZ\[LetterSpace]SCAF\[LetterSpace]MAPKPP\[LetterSpace]POS, v\[LetterSpace]ENZ\[LetterSpace]SCAF\[LetterSpace]MAPK\[LetterSpace]NEG, v\[LetterSpace]ENZ\[LetterSpace]SCAF\[LetterSpace]MAPK\[LetterSpace]POS, v\[LetterSpace]ENZ\[LetterSpace]SCAF\[LetterSpace]MEKPP\[LetterSpace]POS, v\[LetterSpace]ENZ\[LetterSpace]SCAF\[LetterSpace]MEK\[LetterSpace]NEG, v\[LetterSpace]ENZ\[LetterSpace]SCAF\[LetterSpace]MEK\[LetterSpace]POS }; rateEquations = { Reaction1 -> Reaction1\[LetterSpace]a1*RAF[t]*RAFK[t], Reaction10 -> Reaction10\[LetterSpace]a4*MEKp[t]*MEKPH[t], Reaction11 -> Reaction11\[LetterSpace]d4*MEKpMEKPH[t], Reaction12 -> Reaction12\[LetterSpace]k4*MEKpMEKPH[t], Reaction13 -> Reaction13\[LetterSpace]a5*MEKp[t]*RAFp[t], Reaction14 -> Reaction14\[LetterSpace]d5*MEKpRAFp[t], Reaction15 -> Reaction15\[LetterSpace]k5*MEKpRAFp[t], Reaction16 -> Reaction16\[LetterSpace]a6*MEKPH[t]*MEKpp[t], Reaction17 -> Reaction17\[LetterSpace]d6*MEKppMEKPH[t], Reaction18 -> Reaction18\[LetterSpace]k6*MEKppMEKPH[t], Reaction19 -> Reaction19\[LetterSpace]a7*MAPK[t]*MEKpp[t], Reaction2 -> Reaction2\[LetterSpace]d1*RAFRAFK[t], Reaction20 -> Reaction20\[LetterSpace]d7*MAPKMEKpp[t], Reaction21 -> Reaction21\[LetterSpace]k7*MAPKMEKpp[t], Reaction22 -> Reaction22\[LetterSpace]a8*MAPKp[t]*MAPKPH[t], Reaction23 -> Reaction23\[LetterSpace]d8*MAPKpMAPKPH[t], Reaction24 -> Reaction24\[LetterSpace]k8*MAPKpMAPKPH[t], Reaction25 -> Reaction25\[LetterSpace]a9*MAPKp[t]*MEKpp[t], Reaction26 -> Reaction26\[LetterSpace]d9*MAPKpMEKpp[t], Reaction27 -> Reaction27\[LetterSpace]k9*MAPKpMEKpp[t], Reaction28 -> Reaction28\[LetterSpace]a10*MAPKPH[t]*MAPKpp[t], Reaction29 -> Reaction29\[LetterSpace]d10*MAPKppMAPKPH[t], Reaction3 -> Reaction3\[LetterSpace]k1*RAFRAFK[t], Reaction30 -> Reaction30\[LetterSpace]k10*MAPKppMAPKPH[t], Reaction4 -> Reaction4\[LetterSpace]a2*RAFp[t]*RAFPH[t], Reaction5 -> Reaction5\[LetterSpace]d2*RAFpRAFPH[t], Reaction6 -> Reaction6\[LetterSpace]k2*RAFpRAFPH[t], Reaction7 -> Reaction7\[LetterSpace]a3*MEK[t]*RAFp[t], Reaction8 -> Reaction8\[LetterSpace]d3*MEKRAFp[t], Reaction9 -> Reaction9\[LetterSpace]k3*MEKRAFp[t], v\[LetterSpace]ENZ\[LetterSpace]C1\[LetterSpace]NEG -> C1[t]*(on2*MAPK[t] + on1*MEK[t]), v\[LetterSpace]ENZ\[LetterSpace]C1\[LetterSpace]POS -> of1*C2[t] + of3*C3[t] + of2*C4[t] + of4*C5[t], v\[LetterSpace]ENZ\[LetterSpace]C2\[LetterSpace]NEG -> C2[t]*(of1 + on2*MAPK[t]) + kr1*C2[t]*RAFp[t], v\[LetterSpace]ENZ\[LetterSpace]C2\[LetterSpace]POS -> of2*C6[t] + of4*C9[t] + on1*C1[t]*MEK[t], v\[LetterSpace]ENZ\[LetterSpace]C3\[LetterSpace]NEG -> of3*C3[t] + on2*C3[t]*MAPK[t], v\[LetterSpace]ENZ\[LetterSpace]C3\[LetterSpace]POS -> of2*C7[t] + of4*C8[t] + kr1*C2[t]*RAFp[t], v\[LetterSpace]ENZ\[LetterSpace]C4\[LetterSpace]NEG -> C4[t]*(of2 + on1*MEK[t]), v\[LetterSpace]ENZ\[LetterSpace]C4\[LetterSpace]POS -> of1*C6[t] + of3*C7[t] + on2*C1[t]*MAPK[t], v\[LetterSpace]ENZ\[LetterSpace]C5\[LetterSpace]NEG -> C5[t]*(of4 + on1*MEK[t]), v\[LetterSpace]ENZ\[LetterSpace]C5\[LetterSpace]POS -> of3*C8[t] + of1*C9[t], v\[LetterSpace]ENZ\[LetterSpace]C6\[LetterSpace]NEG -> (of1 + of2)*C6[t] + kr1*C6[t]*RAFp[t], v\[LetterSpace]ENZ\[LetterSpace]C6\[LetterSpace]POS -> on2*C2[t]*MAPK[t] + on1*C4[t]*MEK[t], v\[LetterSpace]ENZ\[LetterSpace]C7\[LetterSpace]NEG -> kr2*C7[t] + of2*C7[t] + of3*C7[t], v\[LetterSpace]ENZ\[LetterSpace]C7\[LetterSpace]POS -> on2*C3[t]*MAPK[t] + kr1*C6[t]*RAFp[t], v\[LetterSpace]ENZ\[LetterSpace]C8\[LetterSpace]NEG -> (of3 + of4)*C8[t], v\[LetterSpace]ENZ\[LetterSpace]C8\[LetterSpace]POS -> kr2*C7[t] + kr1*C9[t]*RAFp[t], v\[LetterSpace]ENZ\[LetterSpace]C9\[LetterSpace]NEG -> (of1 + of4)*C9[t] + kr1*C9[t]*RAFp[t], v\[LetterSpace]ENZ\[LetterSpace]C9\[LetterSpace]POS -> on1*C5[t]*MEK[t], v\[LetterSpace]ENZ\[LetterSpace]SCAF\[LetterSpace]MAPKPP\[LetterSpace]POS -> of4*(C5[t] + C8[t] + C9[t]), v\[LetterSpace]ENZ\[LetterSpace]SCAF\[LetterSpace]MAPK\[LetterSpace]NEG -> on2*(C1[t] + C2[t] + C3[t])*MAPK[t], v\[LetterSpace]ENZ\[LetterSpace]SCAF\[LetterSpace]MAPK\[LetterSpace]POS -> of2*(C4[t] + C6[t] + C7[t]), v\[LetterSpace]ENZ\[LetterSpace]SCAF\[LetterSpace]MEKPP\[LetterSpace]POS -> of3*(C3[t] + C7[t] + C8[t]), v\[LetterSpace]ENZ\[LetterSpace]SCAF\[LetterSpace]MEK\[LetterSpace]NEG -> on1*(C1[t] + C4[t] + C5[t])*MEK[t], v\[LetterSpace]ENZ\[LetterSpace]SCAF\[LetterSpace]MEK\[LetterSpace]POS -> of1*(C2[t] + C6[t] + C9[t]) }; parameters = { initial\[LetterSpace]value\[LetterSpace]C1\[LetterSpace]Fraction -> 1.0, initial\[LetterSpace]value\[LetterSpace]C2\[LetterSpace]Fraction -> 0.0, initial\[LetterSpace]value\[LetterSpace]C4\[LetterSpace]Fraction -> 0.0, initial\[LetterSpace]value\[LetterSpace]C6\[LetterSpace]Fraction -> 0.0, initial\[LetterSpace]value\[LetterSpace]MAPK -> 0.4, initial\[LetterSpace]value\[LetterSpace]MEK -> 0.2, initial\[LetterSpace]value\[LetterSpace]RAFK -> 0.2, initial\[LetterSpace]value\[LetterSpace]Total\[LetterSpace]Scaffold -> 0.0, kr1 -> 0.1, kr2 -> 0.1, of1 -> 0.05, of2 -> 0.05, of3 -> 0.05, of4 -> 0.5, on1 -> 10.0, on2 -> 10.0, Reaction1\[LetterSpace]a1 -> 1.0, Reaction10\[LetterSpace]a4 -> 10.0, Reaction11\[LetterSpace]d4 -> 0.8, Reaction12\[LetterSpace]k4 -> 0.1, Reaction13\[LetterSpace]a5 -> 3.3, Reaction14\[LetterSpace]d5 -> 0.4, Reaction15\[LetterSpace]k5 -> 0.1, Reaction16\[LetterSpace]a6 -> 10.0, Reaction17\[LetterSpace]d6 -> 0.8, Reaction18\[LetterSpace]k6 -> 0.1, Reaction19\[LetterSpace]a7 -> 20.0, Reaction2\[LetterSpace]d1 -> 0.4, Reaction20\[LetterSpace]d7 -> 0.6, Reaction21\[LetterSpace]k7 -> 0.1, Reaction22\[LetterSpace]a8 -> 5.0, Reaction23\[LetterSpace]d8 -> 0.4, Reaction24\[LetterSpace]k8 -> 0.1, Reaction25\[LetterSpace]a9 -> 20.0, Reaction26\[LetterSpace]d9 -> 0.6, Reaction27\[LetterSpace]k9 -> 0.1, Reaction28\[LetterSpace]a10 -> 5.0, Reaction29\[LetterSpace]d10 -> 0.4, Reaction3\[LetterSpace]k1 -> 0.1, Reaction30\[LetterSpace]k10 -> 0.1, Reaction4\[LetterSpace]a2 -> 0.5, Reaction5\[LetterSpace]d2 -> 0.5, Reaction6\[LetterSpace]k2 -> 0.1, Reaction7\[LetterSpace]a3 -> 3.3, Reaction8\[LetterSpace]d3 -> 0.42, Reaction9\[LetterSpace]k3 -> 0.1, Cytoplasm -> 1.0 }; assignments = { }; events = { }; speciesAnnotations = { MAPKPH[t]->"http://identifiers.org/uniprot/Q90W58" }; reactionAnnotations = { }; units = { {"time" -> "", "metabolite" -> "", "extent" -> ""} }; (* Time evolution *) odes = { C1'[t] == 1.0*v\[LetterSpace]ENZ\[LetterSpace]C1\[LetterSpace]POS -1.0*v\[LetterSpace]ENZ\[LetterSpace]C1\[LetterSpace]NEG, C2'[t] == 1.0*v\[LetterSpace]ENZ\[LetterSpace]C2\[LetterSpace]POS -1.0*v\[LetterSpace]ENZ\[LetterSpace]C2\[LetterSpace]NEG, C3'[t] == 1.0*v\[LetterSpace]ENZ\[LetterSpace]C3\[LetterSpace]POS -1.0*v\[LetterSpace]ENZ\[LetterSpace]C3\[LetterSpace]NEG, C4'[t] == 1.0*v\[LetterSpace]ENZ\[LetterSpace]C4\[LetterSpace]POS -1.0*v\[LetterSpace]ENZ\[LetterSpace]C4\[LetterSpace]NEG, C5'[t] == 1.0*v\[LetterSpace]ENZ\[LetterSpace]C5\[LetterSpace]POS -1.0*v\[LetterSpace]ENZ\[LetterSpace]C5\[LetterSpace]NEG, C6'[t] == 1.0*v\[LetterSpace]ENZ\[LetterSpace]C6\[LetterSpace]POS -1.0*v\[LetterSpace]ENZ\[LetterSpace]C6\[LetterSpace]NEG, C7'[t] == 1.0*v\[LetterSpace]ENZ\[LetterSpace]C7\[LetterSpace]POS -1.0*v\[LetterSpace]ENZ\[LetterSpace]C7\[LetterSpace]NEG, C8'[t] == 1.0*v\[LetterSpace]ENZ\[LetterSpace]C8\[LetterSpace]POS -1.0*v\[LetterSpace]ENZ\[LetterSpace]C8\[LetterSpace]NEG, C9'[t] == 1.0*v\[LetterSpace]ENZ\[LetterSpace]C9\[LetterSpace]POS -1.0*v\[LetterSpace]ENZ\[LetterSpace]C9\[LetterSpace]NEG, MAPK'[t] == 1.0*Reaction20 +1.0*Reaction24 +1.0*v\[LetterSpace]ENZ\[LetterSpace]SCAF\[LetterSpace]MAPK\[LetterSpace]POS -1.0*Reaction19 -1.0*v\[LetterSpace]ENZ\[LetterSpace]SCAF\[LetterSpace]MAPK\[LetterSpace]NEG, MAPKMEKpp'[t] == 1.0*Reaction19 -1.0*Reaction20 -1.0*Reaction21, MAPKPH'[t] == 1.0*Reaction23 +1.0*Reaction24 +1.0*Reaction29 +1.0*Reaction30 -1.0*Reaction22 -1.0*Reaction28, MAPKp'[t] == 1.0*Reaction21 +1.0*Reaction23 +1.0*Reaction26 +1.0*Reaction30 -1.0*Reaction22 -1.0*Reaction25, MAPKpMAPKPH'[t] == 1.0*Reaction22 -1.0*Reaction23 -1.0*Reaction24, MAPKpMEKpp'[t] == 1.0*Reaction25 -1.0*Reaction26 -1.0*Reaction27, MAPKpp'[t] == 1.0*Reaction27 +1.0*Reaction29 +1.0*v\[LetterSpace]ENZ\[LetterSpace]SCAF\[LetterSpace]MAPKPP\[LetterSpace]POS -1.0*Reaction28, MAPKppMAPKPH'[t] == 1.0*Reaction28 -1.0*Reaction29 -1.0*Reaction30, MEK'[t] == 1.0*Reaction12 +1.0*Reaction8 +1.0*v\[LetterSpace]ENZ\[LetterSpace]SCAF\[LetterSpace]MEK\[LetterSpace]POS -1.0*Reaction7 -1.0*v\[LetterSpace]ENZ\[LetterSpace]SCAF\[LetterSpace]MEK\[LetterSpace]NEG, MEKPH'[t] == 1.0*Reaction11 +1.0*Reaction12 +1.0*Reaction17 +1.0*Reaction18 -1.0*Reaction10 -1.0*Reaction16, MEKRAFp'[t] == 1.0*Reaction7 -1.0*Reaction8 -1.0*Reaction9, MEKp'[t] == 1.0*Reaction11 +1.0*Reaction14 +1.0*Reaction18 +1.0*Reaction9 -1.0*Reaction10 -1.0*Reaction13, MEKpMEKPH'[t] == 1.0*Reaction10 -1.0*Reaction11 -1.0*Reaction12, MEKpRAFp'[t] == 1.0*Reaction13 -1.0*Reaction14 -1.0*Reaction15, MEKpp'[t] == 1.0*Reaction15 +1.0*Reaction17 +1.0*Reaction20 +1.0*Reaction21 +1.0*Reaction26 +1.0*Reaction27 +1.0*v\[LetterSpace]ENZ\[LetterSpace]SCAF\[LetterSpace]MEKPP\[LetterSpace]POS -1.0*Reaction16 -1.0*Reaction19 -1.0*Reaction25, MEKppMEKPH'[t] == 1.0*Reaction16 -1.0*Reaction17 -1.0*Reaction18, RAF'[t] == 1.0*Reaction2 +1.0*Reaction6 -1.0*Reaction1, RAFK'[t] == 1.0*Reaction2 +1.0*Reaction3 -1.0*Reaction1, RAFPH'[t] == 1.0*Reaction5 +1.0*Reaction6 -1.0*Reaction4, RAFRAFK'[t] == 1.0*Reaction1 -1.0*Reaction2 -1.0*Reaction3, RAFp'[t] == 1.0*Reaction14 +1.0*Reaction15 +1.0*Reaction3 +1.0*Reaction5 +1.0*Reaction8 +1.0*Reaction9 -1.0*Reaction13 -1.0*Reaction4 -1.0*Reaction7, RAFpRAFPH'[t] == 1.0*Reaction4 -1.0*Reaction5 -1.0*Reaction6 }; 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]}]