(* 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 = { A[t], B[t], BN[t], Bp[t], D[t], Dusp[t], ERKa[t], ERKt[t], F[t], Fgf[t], K[t], Kt[t], MAx[t], MDusp[t], MF[t], N[t], Na[t], Nan[t], Rasa[t], Rast[t], Xa[t], Xt[t] }; initialValues = { A[0] == 0.1, B[0] == 0.1, BN[0] == 0.001, Bp[0] == 0.1, D[0] == 2.0, Dusp[0] == 0.1, ERKa[0] == 0.2, ERKt[0] == 2.0, F[0] == 0.001, Fgf[0] == 1.0, K[0] == 3.0, Kt[0] == 3.0, MAx[0] == 0.1, MDusp[0] == 0.1, MF[0] == 0.1, N[0] == 0.5, Na[0] == 0.2, Nan[0] == 0.0, Rasa[0] == 0.5, Rast[0] == 2.0, Xa[0] == 0.1, Xt[0] == 2.0 }; rates = { AK\[LetterSpace]dissoc, A\[LetterSpace]degradation, A\[LetterSpace]translation, BP\[LetterSpace]dephosphorylation, B\[LetterSpace]degradation, B\[LetterSpace]phosphorylation, B\[LetterSpace]shuttling, B\[LetterSpace]synth, Bp\[LetterSpace]degradation, Dusp\[LetterSpace]degradation, Dusp\[LetterSpace]translation, Erk\[LetterSpace]activation, Erk\[LetterSpace]inactivation, F\[LetterSpace]degradation, F\[LetterSpace]translation, MAx\[LetterSpace]degradation, MAx\[LetterSpace]trans\[LetterSpace]BN, MAx\[LetterSpace]trans\[LetterSpace]Xa, MAx\[LetterSpace]trans\[LetterSpace]basal, MDusp\[LetterSpace]degradation, MDusp\[LetterSpace]transkription, MF\[LetterSpace]degradation, MF\[LetterSpace]transkription, N\[LetterSpace]activation, N\[LetterSpace]degradation, Na\[LetterSpace]degradation, Na\[LetterSpace]transport, Nan\[LetterSpace]degradation, Ras\[LetterSpace]activation, Ras\[LetterSpace]inactivation, X\[LetterSpace]activation, X\[LetterSpace]inactivation, n\[LetterSpace]synth }; rateEquations = { AK\[LetterSpace]dissoc -> cytosol*theta*(AK*d1 - a1*A[t]*K[t]), A\[LetterSpace]degradation -> (cytosol*theta*vdAx*A[t])/(KdAx + A[t]), A\[LetterSpace]translation -> cytosol*ksAx*theta*MAx[t], BP\[LetterSpace]dephosphorylation -> (cytosol*theta*VMP*Bp[t])/(K2 + Bp[t]), B\[LetterSpace]degradation -> cytosol*kd1*theta*B[t], B\[LetterSpace]phosphorylation -> (AK*cytosol*KID*theta*VMK*B[t])/((K1 + B[t])*(KID + D[t])*Kt[t]), B\[LetterSpace]shuttling -> cytosol*theta*(-(kt3*B[t]) + kt4*BN[t]), B\[LetterSpace]synth -> cytosol*theta*vsB, Bp\[LetterSpace]degradation -> cytosol*kd2*theta*Bp[t], Dusp\[LetterSpace]degradation -> (cytosol*eta*vdDusp*Dusp[t])/(KdDusp + Dusp[t]), Dusp\[LetterSpace]translation -> cytosol*eta*ksDusp*MDusp[t], Erk\[LetterSpace]activation -> (cytosol*ERKi*eta*VMaErk*Rasa[t])/((ERKi + KaErk)*Rast[t]), Erk\[LetterSpace]inactivation -> (cytosol*eta*kcDusp*Dusp[t]*ERKa[t])/(KdErk + ERKa[t]), F\[LetterSpace]degradation -> (cytosol*epsilon*vdF*F[t])/(KdF + F[t]), F\[LetterSpace]translation -> cytosol*epsilon*ksF*MF[t], MAx\[LetterSpace]degradation -> (cytosol*theta*vmd*MAx[t])/(Kmd + MAx[t]), MAx\[LetterSpace]trans\[LetterSpace]BN -> (cytosol*theta*vMB*BN[t]^n)/(KaB^n + BN[t]^n), MAx\[LetterSpace]trans\[LetterSpace]Xa -> (cytosol*theta*vMXa*Xa[t]^m)/(KaXa^m + Xa[t]^m), MAx\[LetterSpace]trans\[LetterSpace]basal -> cytosol*theta*v0, MDusp\[LetterSpace]degradation -> (cytosol*eta*VMdMDusp*MDusp[t])/(KdMDusp + MDusp[t]), MDusp\[LetterSpace]transkription -> (cytosol*eta*VMsMDusp*Xa[t]^q)/(KaMDusp^q + Xa[t]^q), MF\[LetterSpace]degradation -> (cytosol*epsilon*vmF*MF[t])/(KdMF + MF[t]), MF\[LetterSpace]transkription -> (cytosol*epsilon*vsFK*Nan[t]^p)/(KA^p + Nan[t]^p), N\[LetterSpace]activation -> (cytosol*epsilon*kc*KIF^j*N[t])/(KIF^j + F[t]^j), N\[LetterSpace]degradation -> (cytosol*epsilon*vdN*N[t])/(KdN + N[t]), Na\[LetterSpace]degradation -> (cytosol*epsilon*VdNa*Na[t])/(KdNa + Na[t]), Na\[LetterSpace]transport -> cytosol*epsilon*(kt1*Na[t] - kt2*Nan[t]), Nan\[LetterSpace]degradation -> (cytosol*epsilon*VdNan*Nan[t])/(KdNan + Nan[t]), Ras\[LetterSpace]activation -> (cytosol*eta*Rasi*VMaRas*Fgf[t]^r)/((KaRas + Rasi)*(KaFgf^r + Fgf[t]^r)), Ras\[LetterSpace]inactivation -> (cytosol*eta*VMdRas*Rasa[t])/(KdRas + Rasa[t]), X\[LetterSpace]activation -> (cytosol*eta*VMaX*Xi*ERKa[t])/((KaX + Xi)*ERKt[t]), X\[LetterSpace]inactivation -> (cytosol*eta*VMdX*Xa[t])/(KdX + Xa[t]), n\[LetterSpace]synth -> cytosol*epsilon*vsN }; parameters = { K1 -> 0.28, K2 -> 0.03, KA -> 0.05, KID -> 0.5, KIF -> 0.5, KIG1 -> 2.5, KaB -> 0.7, KaErk -> 0.05, KaFgf -> 0.5, KaMDusp -> 0.5, KaRas -> 0.103, KaX -> 0.05, KaXa -> 0.05, KdAx -> 0.63, KdDusp -> 0.5, KdErk -> 0.05, KdF -> 0.37, KdMDusp -> 0.5, KdMF -> 0.768, KdN -> 1.4, KdNa -> 0.001, KdNan -> 0.001, KdRas -> 0.1, KdX -> 0.05, Kmd -> 0.48, VMK -> 5.08, VMP -> 1.0, VMaErk -> 3.3, VMaRas -> 4.968, VMaX -> 1.6, VMdMDusp -> 0.5, VMdRas -> 0.41, VMdX -> 0.5, VMsMDusp -> 0.9, VdNa -> 0.01, VdNan -> 0.1, a1 -> 1.8, d1 -> 0.1, epsilon -> 0.3, eta -> 0.3, j -> 2.0, kc -> 3.45, kcDusp -> 1.35, kd1 -> 0.0, kd2 -> 7.062, ksAx -> 0.02, ksDusp -> 0.5, ksF -> 0.3, kt1 -> 0.1, kt2 -> 0.1, kt3 -> 0.7, kt4 -> 1.5, m -> 2.0, n -> 2.0, p -> 2.0, q -> 2.0, r -> 2.0, theta -> 1.5, v0 -> 0.06, vMB -> 1.64, vMXa -> 0.5, vdAx -> 0.6, vdDusp -> 2.0, vdF -> 0.39, vdN -> 2.82, vmF -> 1.92, vmd -> 0.8, vsB -> 0.087, vsF -> 3.0, vsN -> 0.23, cytosol -> 1.0 }; assignments = { Xi -> -Xa[t] + Xt[t], ERKi -> -ERKa[t] + ERKt[t], Rasi -> -Rasa[t] + Rast[t], AK -> -K[t] + Kt[t], vsFK -> (KIG1*vsF)/(KIG1 + K[t]) }; events = { }; speciesAnnotations = { }; reactionAnnotations = { }; units = { {"time" -> "", "metabolite" -> "/litre", "extent" -> "/litre"} }; (* Time evolution *) odes = { A'[t] == 1.0*AK\[LetterSpace]dissoc +1.0*A\[LetterSpace]translation -1.0*A\[LetterSpace]degradation, B'[t] == 1.0*B\[LetterSpace]synth +1.0*BP\[LetterSpace]dephosphorylation +1.0*B\[LetterSpace]shuttling -1.0*B\[LetterSpace]degradation -1.0*B\[LetterSpace]phosphorylation, BN'[t] == -1.0*B\[LetterSpace]shuttling, Bp'[t] == 1.0*B\[LetterSpace]phosphorylation -1.0*BP\[LetterSpace]dephosphorylation -1.0*Bp\[LetterSpace]degradation, D'[t] == 0.0 , Dusp'[t] == 1.0*Dusp\[LetterSpace]translation -1.0*Dusp\[LetterSpace]degradation, ERKa'[t] == 1.0*Erk\[LetterSpace]activation -1.0*Erk\[LetterSpace]inactivation, ERKt'[t] == 0.0 , F'[t] == 1.0*F\[LetterSpace]translation -1.0*F\[LetterSpace]degradation, Fgf'[t] == 0.0 , K'[t] == 1.0*AK\[LetterSpace]dissoc , Kt'[t] == 0.0 , MAx'[t] == 1.0*MAx\[LetterSpace]trans\[LetterSpace]basal +1.0*MAx\[LetterSpace]trans\[LetterSpace]BN +1.0*MAx\[LetterSpace]trans\[LetterSpace]Xa -1.0*MAx\[LetterSpace]degradation, MDusp'[t] == 1.0*MDusp\[LetterSpace]transkription -1.0*MDusp\[LetterSpace]degradation, MF'[t] == 1.0*MF\[LetterSpace]transkription -1.0*MF\[LetterSpace]degradation, N'[t] == 1.0*n\[LetterSpace]synth -1.0*N\[LetterSpace]degradation -1.0*N\[LetterSpace]activation, Na'[t] == 1.0*N\[LetterSpace]activation -1.0*Na\[LetterSpace]degradation -1.0*Na\[LetterSpace]transport, Nan'[t] == 1.0*Na\[LetterSpace]transport -1.0*Nan\[LetterSpace]degradation, Rasa'[t] == 1.0*Ras\[LetterSpace]activation -1.0*Ras\[LetterSpace]inactivation, Rast'[t] == 0.0 , Xa'[t] == 1.0*X\[LetterSpace]activation -1.0*X\[LetterSpace]inactivation, Xt'[t] == 0.0 }; 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]}]