(* 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 = { Akt[t], AktPIP[t], AktPIP3[t], AktPIPP[t], E[t], ERK[t], ERKP[t], ERKPP[t], GS[t], HRG[t], MEK[t], MEKP[t], MEKPP[t], MKP3[t], PI3K[t], PI3Kstar[t], PIP3[t], PP2A[t], P\[LetterSpace]I[t], R[t], RHRG[t], RHRG2[t], RP[t], RPI3K[t], RPI3Kstar[t], RShGS[t], RShP[t], RShc[t], Raf[t], Rafstar[t], RasGDP[t], RasGTP[t], ShGS[t], ShP[t], Shc[t], internalization[t] }; initialValues = { Akt[0] == 10.0, AktPIP[0] == 0.0, AktPIP3[0] == 0.0, AktPIPP[0] == 0.0, E[0] == 7.0, ERK[0] == 1000.0, ERKP[0] == 0.0, ERKPP[0] == 0.0, GS[0] == 10.0, HRG[0] == 330.0, MEK[0] == 120.0, MEKP[0] == 0.0, MEKPP[0] == 0.0, MKP3[0] == 2.4, PI3K[0] == 10.0, PI3Kstar[0] == 0.0, PIP3[0] == 0.0, PP2A[0] == 11.4, P\[LetterSpace]I[0] == 800.0, R[0] == 80.0, RHRG[0] == 0.0, RHRG2[0] == 0.0, RP[0] == 0.0, RPI3K[0] == 0.0, RPI3Kstar[0] == 0.0, RShGS[0] == 0.0, RShP[0] == 0.0, RShc[0] == 0.0, Raf[0] == 100.0, Rafstar[0] == 0.0, RasGDP[0] == 120.0, RasGTP[0] == 0.0, ShGS[0] == 0.0, ShP[0] == 0.0, Shc[0] == 1000.0, internalization[0] == 0.0 }; rates = { reaction\[LetterSpace]0000001, reaction\[LetterSpace]0000002, reaction\[LetterSpace]0000003, reaction\[LetterSpace]0000004, reaction\[LetterSpace]0000005, reaction\[LetterSpace]0000006, reaction\[LetterSpace]0000007, reaction\[LetterSpace]0000008, reaction\[LetterSpace]0000009, reaction\[LetterSpace]0000010, reaction\[LetterSpace]0000011, reaction\[LetterSpace]0000012, reaction\[LetterSpace]0000013, reaction\[LetterSpace]0000014, reaction\[LetterSpace]0000015, reaction\[LetterSpace]0000016, reaction\[LetterSpace]0000017, reaction\[LetterSpace]0000018, reaction\[LetterSpace]0000019, reaction\[LetterSpace]0000020, reaction\[LetterSpace]0000021, reaction\[LetterSpace]0000022, reaction\[LetterSpace]0000023, reaction\[LetterSpace]0000024, reaction\[LetterSpace]0000025, reaction\[LetterSpace]0000026, reaction\[LetterSpace]0000027, reaction\[LetterSpace]0000028, reaction\[LetterSpace]0000029, reaction\[LetterSpace]0000030, reaction\[LetterSpace]0000031, reaction\[LetterSpace]0000032, reaction\[LetterSpace]0000033, reaction\[LetterSpace]0000034 }; rateEquations = { reaction\[LetterSpace]0000001 -> compartment\[LetterSpace]0000001*(k1*HRG[t]*R[t] - k\[LetterSpace]1*RHRG[t]), reaction\[LetterSpace]0000002 -> compartment\[LetterSpace]0000001*(k2*RHRG[t]^2 - k\[LetterSpace]2*RHRG2[t]), reaction\[LetterSpace]0000003 -> compartment\[LetterSpace]0000001*(k3*RHRG2[t] - k\[LetterSpace]3*RP[t]), reaction\[LetterSpace]0000004 -> (compartment\[LetterSpace]0000001*V4*RP[t])/(K4 + RP[t]), reaction\[LetterSpace]0000005 -> compartment\[LetterSpace]0000001*(-(k\[LetterSpace]5*RShc[t]) + k5*RP[t]*Shc[t]), reaction\[LetterSpace]0000006 -> compartment\[LetterSpace]0000001*(k6*RShc[t] - k\[LetterSpace]6*RShP[t]), reaction\[LetterSpace]0000007 -> compartment\[LetterSpace]0000001*(-(k\[LetterSpace]7*RShGS[t]) + k7*GS[t]*RShP[t]), reaction\[LetterSpace]0000008 -> compartment\[LetterSpace]0000001*(k8*RShGS[t] - k\[LetterSpace]8*RP[t]*ShGS[t]), reaction\[LetterSpace]0000009 -> compartment\[LetterSpace]0000001*(k9*ShGS[t] - k\[LetterSpace]9*GS[t]*ShP[t]), reaction\[LetterSpace]0000010 -> (compartment\[LetterSpace]0000001*V10*ShP[t])/(K10 + ShP[t]), reaction\[LetterSpace]0000011 -> (compartment\[LetterSpace]0000001*k11*RasGDP[t]*ShGS[t])/(K11 + RasGDP[t]), reaction\[LetterSpace]0000012 -> (compartment\[LetterSpace]0000001*V12*RasGTP[t])/(K12 + RasGTP[t]), reaction\[LetterSpace]0000013 -> (compartment\[LetterSpace]0000001*k13*Raf[t]*RasGTP[t])/(K13 + Raf[t]), reaction\[LetterSpace]0000014 -> (compartment\[LetterSpace]0000001*k14*(AktPIPP[t] + E[t])*Rafstar[t])/(K14 + Rafstar[t]), reaction\[LetterSpace]0000015 -> (compartment\[LetterSpace]0000001*k15*MEK[t]*Rafstar[t])/(MEK[t] + K15*(1 + MEKP[t]/K17)), reaction\[LetterSpace]0000016 -> (compartment\[LetterSpace]0000001*k16*MEKP[t]*PP2A[t])/(MEKP[t] + K16*(1 + AktPIP[t]/K31 + AktPIPP[t]/K33 + MEKPP[t]/K18)), reaction\[LetterSpace]0000017 -> (compartment\[LetterSpace]0000001*k17*MEKP[t]*Rafstar[t])/(K17*(1 + MEK[t]/K15) + MEKP[t]), reaction\[LetterSpace]0000018 -> (compartment\[LetterSpace]0000001*k18*MEKPP[t]*PP2A[t])/(K18*(1 + AktPIPP[t]/K31 + AktPIPP[t]/K33 + MEKP[t]/K16) + MEKPP[t]), reaction\[LetterSpace]0000019 -> (compartment\[LetterSpace]0000001*k19*ERK[t]*MEKPP[t])/(ERK[t] + K19*(1 + ERKP[t]/K21)), reaction\[LetterSpace]0000020 -> (compartment\[LetterSpace]0000001*k20*ERKP[t]*MKP3[t])/(ERKP[t] + K20*(1 + ERKPP[t]/K22)), reaction\[LetterSpace]0000021 -> (compartment\[LetterSpace]0000001*k21*ERKP[t]*MEKPP[t])/(K21*(1 + ERK[t]/K19) + ERKP[t]), reaction\[LetterSpace]0000022 -> (compartment\[LetterSpace]0000001*k22*ERKPP[t]*MKP3[t])/(K22*(1 + ERKP[t]/K20) + ERKPP[t]), reaction\[LetterSpace]0000023 -> compartment\[LetterSpace]0000001*(k23*PI3K[t]*RP[t] - k\[LetterSpace]23*RPI3K[t]), reaction\[LetterSpace]0000024 -> compartment\[LetterSpace]0000001*(k24*RPI3K[t] - k\[LetterSpace]24*RPI3Kstar[t]), reaction\[LetterSpace]0000025 -> compartment\[LetterSpace]0000001*(-(k\[LetterSpace]25*PI3Kstar[t]*RP[t]) + k25*RPI3Kstar[t]), reaction\[LetterSpace]0000026 -> (compartment\[LetterSpace]0000001*V26*PI3Kstar[t])/(K26 + PI3Kstar[t]), reaction\[LetterSpace]0000027 -> (compartment\[LetterSpace]0000001*k27*PI3Kstar[t]*P\[LetterSpace]I[t])/(K27 + P\[LetterSpace]I[t]), reaction\[LetterSpace]0000028 -> (compartment\[LetterSpace]0000001*V28*PIP3[t])/(K28 + PIP3[t]), reaction\[LetterSpace]0000029 -> compartment\[LetterSpace]0000001*(-(k\[LetterSpace]29*AktPIP3[t]) + k29*Akt[t]*PIP3[t]), reaction\[LetterSpace]0000030 -> (compartment\[LetterSpace]0000001*V30*AktPIP3[t])/(K30*(1 + AktPIP[t]/K32) + AktPIP3[t]), reaction\[LetterSpace]0000031 -> (compartment\[LetterSpace]0000001*k31*AktPIP[t]*PP2A[t])/(AktPIP[t] + K31*(1 + AktPIPP[t]/K33 + MEKP[t]/K16 + MEKPP[t]/K18)), reaction\[LetterSpace]0000032 -> (compartment\[LetterSpace]0000001*V32*AktPIP[t])/(AktPIP[t] + K32*(1 + AktPIP3[t]/K30)), reaction\[LetterSpace]0000033 -> (compartment\[LetterSpace]0000001*k33*AktPIPP[t]*PP2A[t])/(AktPIPP[t] + K33*(1 + AktPIP[t]/K31 + MEKP[t]/K16 + MEKPP[t]/K18)), reaction\[LetterSpace]0000034 -> compartment\[LetterSpace]0000001*(-(k\[LetterSpace]34*internalization[t]) + k34*RP[t]) }; parameters = { K10 -> 340.0, K11 -> 0.181, K12 -> 0.0571, K13 -> 11.7, K14 -> 8.07, K15 -> 317.0, K16 -> 2200.0, K17 -> 317.0, K18 -> 60.0, K19 -> 146000.0, K20 -> 160.0, K21 -> 146000.0, K22 -> 60.0, K26 -> 3680.0, K27 -> 39.1, K28 -> 9.02, K30 -> 80000.0, K31 -> 4.35, K32 -> 80000.0, K33 -> 12.0, K4 -> 50.0, V10 -> 0.0154, V12 -> 0.289, V26 -> 2620.0, V28 -> 17000.0, V30 -> 20000.0, V32 -> 20000.0, V4 -> 62.5, k1 -> 0.0012, k11 -> 0.222, k13 -> 1.53, k14 -> 0.00673, k15 -> 3.5, k16 -> 0.058, k17 -> 2.9, k18 -> 0.058, k19 -> 9.5, k2 -> 0.01, k20 -> 0.3, k21 -> 16.0, k22 -> 0.27, k23 -> 0.1, k24 -> 9.85, k25 -> 45.8, k27 -> 16.9, k29 -> 507.0, k3 -> 1.0, k31 -> 0.107, k33 -> 0.211, k34 -> 0.001, k5 -> 0.1, k6 -> 20.0, k7 -> 60.0, k8 -> 2040.0, k9 -> 40.8, k\[LetterSpace]1 -> 0.00076, k\[LetterSpace]2 -> 0.1, k\[LetterSpace]23 -> 2.0, k\[LetterSpace]24 -> 0.0985, k\[LetterSpace]25 -> 0.047, k\[LetterSpace]29 -> 234.0, k\[LetterSpace]3 -> 0.01, k\[LetterSpace]34 -> 0.0, k\[LetterSpace]5 -> 1.0, k\[LetterSpace]6 -> 5.0, k\[LetterSpace]7 -> 546.0, k\[LetterSpace]8 -> 15700.0, k\[LetterSpace]9 -> 0.0, compartment\[LetterSpace]0000001 -> 1.0 }; assignments = { MEKPP\[LetterSpace]percent -> (5*MEKPP[t])/6, AktPP\[LetterSpace]percent -> 10*AktPIPP[t], ERKPP\[LetterSpace]percent -> ERKPP[t]/10, Rafstar\[LetterSpace]percent -> Rafstar[t], PI3Kstar\[LetterSpace]percent -> 10*PI3Kstar[t], ShP\[LetterSpace]percent -> ShP[t]/10, RP\[LetterSpace]percent -> (5*(RP[t] + RPI3K[t] + RPI3Kstar[t] + RShc[t] + RShGS[t] + RShP[t]))/2 }; events = { }; speciesAnnotations = { PIP3[t]->"http://identifiers.org/chebi/CHEBI:16618", P\[LetterSpace]I[t]->"http://identifiers.org/chebi/CHEBI:26034" }; reactionAnnotations = { }; units = { {"time" -> "", "metabolite" -> "", "extent" -> ""} }; (* Time evolution *) odes = { Akt'[t] == -1.0*reaction\[LetterSpace]0000029, AktPIP'[t] == 1.0*reaction\[LetterSpace]0000030 +1.0*reaction\[LetterSpace]0000033 -1.0*reaction\[LetterSpace]0000031 -1.0*reaction\[LetterSpace]0000032, AktPIP3'[t] == 1.0*reaction\[LetterSpace]0000029 +1.0*reaction\[LetterSpace]0000031 -1.0*reaction\[LetterSpace]0000030, AktPIPP'[t] == 1.0*reaction\[LetterSpace]0000032 -1.0*reaction\[LetterSpace]0000033, E'[t] == 0.0 , ERK'[t] == 1.0*reaction\[LetterSpace]0000020 -1.0*reaction\[LetterSpace]0000019, ERKP'[t] == 1.0*reaction\[LetterSpace]0000019 +1.0*reaction\[LetterSpace]0000022 -1.0*reaction\[LetterSpace]0000020 -1.0*reaction\[LetterSpace]0000021, ERKPP'[t] == 1.0*reaction\[LetterSpace]0000021 -1.0*reaction\[LetterSpace]0000022, GS'[t] == 1.0*reaction\[LetterSpace]0000009 -1.0*reaction\[LetterSpace]0000007, HRG'[t] == -1.0*reaction\[LetterSpace]0000001, MEK'[t] == 1.0*reaction\[LetterSpace]0000016 -1.0*reaction\[LetterSpace]0000015, MEKP'[t] == 1.0*reaction\[LetterSpace]0000015 +1.0*reaction\[LetterSpace]0000018 -1.0*reaction\[LetterSpace]0000016 -1.0*reaction\[LetterSpace]0000017, MEKPP'[t] == 1.0*reaction\[LetterSpace]0000017 -1.0*reaction\[LetterSpace]0000018, MKP3'[t] == 0.0 , PI3K'[t] == 1.0*reaction\[LetterSpace]0000026 -1.0*reaction\[LetterSpace]0000023, PI3Kstar'[t] == 1.0*reaction\[LetterSpace]0000025 -1.0*reaction\[LetterSpace]0000026, PIP3'[t] == 1.0*reaction\[LetterSpace]0000027 -1.0*reaction\[LetterSpace]0000029 -1.0*reaction\[LetterSpace]0000028, PP2A'[t] == 0.0 , P\[LetterSpace]I'[t] == 1.0*reaction\[LetterSpace]0000028 -1.0*reaction\[LetterSpace]0000027, R'[t] == -1.0*reaction\[LetterSpace]0000001, RHRG'[t] == 1.0*reaction\[LetterSpace]0000001 -2.0*reaction\[LetterSpace]0000002, RHRG2'[t] == 1.0*reaction\[LetterSpace]0000002 +1.0*reaction\[LetterSpace]0000004 -1.0*reaction\[LetterSpace]0000003, RP'[t] == 1.0*reaction\[LetterSpace]0000003 +1.0*reaction\[LetterSpace]0000008 +1.0*reaction\[LetterSpace]0000025 -1.0*reaction\[LetterSpace]0000004 -1.0*reaction\[LetterSpace]0000005 -1.0*reaction\[LetterSpace]0000023 -1.0*reaction\[LetterSpace]0000034, RPI3K'[t] == 1.0*reaction\[LetterSpace]0000023 -1.0*reaction\[LetterSpace]0000024, RPI3Kstar'[t] == 1.0*reaction\[LetterSpace]0000024 -1.0*reaction\[LetterSpace]0000025, RShGS'[t] == 1.0*reaction\[LetterSpace]0000007 -1.0*reaction\[LetterSpace]0000008, RShP'[t] == 1.0*reaction\[LetterSpace]0000006 -1.0*reaction\[LetterSpace]0000007, RShc'[t] == 1.0*reaction\[LetterSpace]0000005 -1.0*reaction\[LetterSpace]0000006, Raf'[t] == 1.0*reaction\[LetterSpace]0000014 -1.0*reaction\[LetterSpace]0000013, Rafstar'[t] == 1.0*reaction\[LetterSpace]0000013 -1.0*reaction\[LetterSpace]0000014, RasGDP'[t] == 1.0*reaction\[LetterSpace]0000012 -1.0*reaction\[LetterSpace]0000011, RasGTP'[t] == 1.0*reaction\[LetterSpace]0000011 -1.0*reaction\[LetterSpace]0000012, ShGS'[t] == 1.0*reaction\[LetterSpace]0000008 -1.0*reaction\[LetterSpace]0000009, ShP'[t] == 1.0*reaction\[LetterSpace]0000009 -1.0*reaction\[LetterSpace]0000010, Shc'[t] == 1.0*reaction\[LetterSpace]0000010 -1.0*reaction\[LetterSpace]0000005, internalization'[t] == 1.0*reaction\[LetterSpace]0000034 }; 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]}]