(* 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 = { Active\[LetterSpace]R2[t], Active\[LetterSpace]Rec[t], Active\[LetterSpace]Rec\[LetterSpace]endo[t], Inactive\[LetterSpace]Rec[t], S2\[LetterSpace]c[t], S2\[LetterSpace]n[t], S4\[LetterSpace]c[t], S4\[LetterSpace]n[t], S7[t], Smad7mRNA[t], Smad7mRNA1[t], TGFb[t], TGFb\[LetterSpace]In[t], TGFb\[LetterSpace]R1\[LetterSpace]endo[t], TGFb\[LetterSpace]R1\[LetterSpace]surface[t], TGFb\[LetterSpace]R2\[LetterSpace]endo[t], TGFb\[LetterSpace]R2\[LetterSpace]surface[t], pS2\[LetterSpace]c[t], pS2\[LetterSpace]n[t], pS2\[LetterSpace]pS2\[LetterSpace]S4\[LetterSpace]c[t], pS2\[LetterSpace]pS2\[LetterSpace]S4\[LetterSpace]n[t], pS2\[LetterSpace]pS2\[LetterSpace]pS2\[LetterSpace]c[t], pS2\[LetterSpace]pS2\[LetterSpace]pS2\[LetterSpace]n[t] }; initialValues = { Active\[LetterSpace]R2[0] == 0.0, Active\[LetterSpace]Rec[0] == 0.0, Active\[LetterSpace]Rec\[LetterSpace]endo[0] == 0.0, Inactive\[LetterSpace]Rec[0] == 0.0, S2\[LetterSpace]c[0] == 638.6434569983527, S2\[LetterSpace]n[0] == 237.39868237428928, S4\[LetterSpace]c[0] == 460.47553390898076, S4\[LetterSpace]n[0] == 169.41748794160233, S7[0] == 12.043365220732587, Smad7mRNA[0] == 0.05642005114580563, Smad7mRNA1[0] == 0.3670825118716101, TGFb[0] == 0.0, TGFb\[LetterSpace]In[0] == 0.0, TGFb\[LetterSpace]R1\[LetterSpace]endo[0] == 18.76309651441349, TGFb\[LetterSpace]R1\[LetterSpace]surface[0] == 16.109716026084108, TGFb\[LetterSpace]R2\[LetterSpace]endo[0] == 28.058081318683687, TGFb\[LetterSpace]R2\[LetterSpace]surface[0] == 6.941118732445909, pS2\[LetterSpace]c[0] == 0.0, pS2\[LetterSpace]n[0] == 0.0, pS2\[LetterSpace]pS2\[LetterSpace]S4\[LetterSpace]c[0] == 0.0, pS2\[LetterSpace]pS2\[LetterSpace]S4\[LetterSpace]n[0] == 0.0, pS2\[LetterSpace]pS2\[LetterSpace]pS2\[LetterSpace]c[0] == 0.0, pS2\[LetterSpace]pS2\[LetterSpace]pS2\[LetterSpace]n[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, reaction31, reaction32, reaction33, reaction34, reaction35, reaction36, reaction37, reaction38, reaction39, reaction4, reaction40, reaction41, reaction42, reaction43, reaction44, reaction45, reaction46, reaction47, reaction5, reaction50, reaction51, reaction52, reaction53, reaction54, reaction55, reaction56, reaction57, reaction58, reaction59, reaction6, reaction60, reaction61, reaction62, reaction63, reaction64, reaction65, reaction66, reaction67, reaction68, reaction7, reaction8, reaction9 }; rateEquations = { reaction1 -> cyt*Function\[LetterSpace]for\[LetterSpace]reaction1\[LetterSpace]0[TGFb[t], TGFb\[LetterSpace]R2\[LetterSpace]surface[t], k\[LetterSpace]medium, kf\[LetterSpace]R2\[LetterSpace]activation], reaction10 -> cyt*kdeg\[LetterSpace]R1*Active\[LetterSpace]Rec\[LetterSpace]endo[t], reaction11 -> cyt*kin\[LetterSpace]deg\[LetterSpace]Ligand*Active\[LetterSpace]Rec\[LetterSpace]endo[t], reaction12 -> cyt*kdeg\[LetterSpace]R1*TGFb\[LetterSpace]R1\[LetterSpace]endo[t], reaction13 -> cyt*kdeg\[LetterSpace]R2*TGFb\[LetterSpace]R2\[LetterSpace]endo[t], reaction14 -> cyt*kf\[LetterSpace]Seq\[LetterSpace]S7\[LetterSpace]Rec*Active\[LetterSpace]Rec[t]*S7[t], reaction15 -> cyt*Function\[LetterSpace]for\[LetterSpace]reaction15\[LetterSpace]0[Inactive\[LetterSpace]Rec[t], index\[LetterSpace]seq\[LetterSpace]kb, kf\[LetterSpace]Seq\[LetterSpace]S7\[LetterSpace]Rec], reaction16 -> cyt*Function\[LetterSpace]for\[LetterSpace]reaction16\[LetterSpace]0[Inactive\[LetterSpace]Rec[t], index\[LetterSpace]induced\[LetterSpace]ligand\[LetterSpace]deg, kin\[LetterSpace]deg\[LetterSpace]Ligand], reaction17 -> cyt*Function\[LetterSpace]for\[LetterSpace]reaction17\[LetterSpace]0[Inactive\[LetterSpace]Rec[t], index\[LetterSpace]induced\[LetterSpace]R2\[LetterSpace]deg, kdeg\[LetterSpace]R2], reaction18 -> cyt*k\[LetterSpace]in\[LetterSpace]1*TGFb\[LetterSpace]R1\[LetterSpace]surface[t], reaction19 -> cyt*k\[LetterSpace]in\[LetterSpace]2*TGFb\[LetterSpace]R2\[LetterSpace]surface[t], reaction2 -> cyt*Function\[LetterSpace]for\[LetterSpace]reaction2\[LetterSpace]0[TGFb[t], TGFb\[LetterSpace]R2\[LetterSpace]surface[t], kf\[LetterSpace]R2\[LetterSpace]activation], reaction20 -> cyt*Function\[LetterSpace]for\[LetterSpace]reaction20\[LetterSpace]3\[LetterSpace]0[TGFb\[LetterSpace]R1\[LetterSpace]endo[t], index\[LetterSpace]k\[LetterSpace]out\[LetterSpace]1\[LetterSpace]relative\[LetterSpace]speed, k\[LetterSpace]in\[LetterSpace]1], reaction21 -> cyt*Function\[LetterSpace]for\[LetterSpace]reaction21\[LetterSpace]3\[LetterSpace]0[TGFb\[LetterSpace]R2\[LetterSpace]endo[t], index\[LetterSpace]k\[LetterSpace]out\[LetterSpace]2\[LetterSpace]relative\[LetterSpace]speed, k\[LetterSpace]in\[LetterSpace]2], reaction22 -> cyt*Function\[LetterSpace]for\[LetterSpace]reaction22\[LetterSpace]3\[LetterSpace]0[Active\[LetterSpace]Rec[t], index\[LetterSpace]active\[LetterSpace]Rec\[LetterSpace]internalize, k\[LetterSpace]in\[LetterSpace]1], reaction23 -> cyt*k\[LetterSpace]disso\[LetterSpace]Active\[LetterSpace]Rec*Active\[LetterSpace]Rec\[LetterSpace]endo[t], reaction24 -> cyt*kin\[LetterSpace]deg\[LetterSpace]Ligand*TGFb\[LetterSpace]In[t], reaction25 -> cyt*Function\[LetterSpace]for\[LetterSpace]reaction25\[LetterSpace]\[LetterSpace]1\[LetterSpace]0[Active\[LetterSpace]Rec\[LetterSpace]endo[t], S2\[LetterSpace]c[t], k\[LetterSpace]phosphorylation], reaction26 -> cyt*kf\[LetterSpace]trimmer*pS2\[LetterSpace]c[t]^2*S4\[LetterSpace]c[t], reaction27 -> cyt*kb\[LetterSpace]trimmer*pS2\[LetterSpace]pS2\[LetterSpace]S4\[LetterSpace]c[t], reaction28 -> kf\[LetterSpace]trimmer*nuc*pS2\[LetterSpace]n[t]^2*S4\[LetterSpace]n[t], reaction29 -> kb\[LetterSpace]trimmer*nuc*pS2\[LetterSpace]pS2\[LetterSpace]S4\[LetterSpace]n[t], reaction3 -> cyt*Function\[LetterSpace]for\[LetterSpace]reaction3\[LetterSpace]0[TGFb[t], TGFb\[LetterSpace]R2\[LetterSpace]surface[t], kf\[LetterSpace]R2\[LetterSpace]activation], reaction30 -> cyt*Function\[LetterSpace]for\[LetterSpace]reaction30\[LetterSpace]0[index\[LetterSpace]kf\[LetterSpace]homotrimer, kf\[LetterSpace]trimmer, pS2\[LetterSpace]c[t]], reaction31 -> nuc*Function\[LetterSpace]for\[LetterSpace]reaction31\[LetterSpace]1\[LetterSpace]0[index\[LetterSpace]kf\[LetterSpace]homotrimer, kf\[LetterSpace]trimmer, pS2\[LetterSpace]n[t]], reaction32 -> nuc*Function\[LetterSpace]for\[LetterSpace]reaction32\[LetterSpace]2\[LetterSpace]0[index\[LetterSpace]kb\[LetterSpace]homotrimer, kb\[LetterSpace]trimmer, pS2\[LetterSpace]pS2\[LetterSpace]pS2\[LetterSpace]n[t]], reaction33 -> cyt*Function\[LetterSpace]for\[LetterSpace]reaction33\[LetterSpace]3\[LetterSpace]0[index\[LetterSpace]kb\[LetterSpace]homotrimer, kb\[LetterSpace]trimmer, pS2\[LetterSpace]pS2\[LetterSpace]pS2\[LetterSpace]c[t]], reaction34 -> Function\[LetterSpace]for\[LetterSpace]reaction34\[LetterSpace]3\[LetterSpace]0[S2\[LetterSpace]c[t], S2\[LetterSpace]import\[LetterSpace]to\[LetterSpace]nuc, cyt], reaction35 -> Function\[LetterSpace]for\[LetterSpace]reaction35\[LetterSpace]4\[LetterSpace]0[S2\[LetterSpace]export\[LetterSpace]from\[LetterSpace]nuc, S2\[LetterSpace]n[t], nuc], reaction36 -> Function\[LetterSpace]for\[LetterSpace]reaction36\[LetterSpace]4\[LetterSpace]0[S4\[LetterSpace]c[t], S4\[LetterSpace]import\[LetterSpace]to\[LetterSpace]nuc, cyt], reaction37 -> Function\[LetterSpace]for\[LetterSpace]reaction37\[LetterSpace]4\[LetterSpace]0[S4\[LetterSpace]export\[LetterSpace]from\[LetterSpace]nuc, S4\[LetterSpace]n[t], nuc], reaction38 -> Function\[LetterSpace]for\[LetterSpace]reaction38\[LetterSpace]4\[LetterSpace]0[S2\[LetterSpace]import\[LetterSpace]to\[LetterSpace]nuc, cyt, pS2\[LetterSpace]c[t]], reaction39 -> Function\[LetterSpace]for\[LetterSpace]reaction39\[LetterSpace]4\[LetterSpace]0[S2\[LetterSpace]export\[LetterSpace]from\[LetterSpace]nuc, nuc, pS2\[LetterSpace]n[t]], reaction4 -> cyt*Function\[LetterSpace]for\[LetterSpace]reaction4\[LetterSpace]0[Active\[LetterSpace]R2[t], index\[LetterSpace]kb\[LetterSpace]R2, kf\[LetterSpace]R2\[LetterSpace]activation], reaction40 -> Function\[LetterSpace]for\[LetterSpace]reaction40\[LetterSpace]4\[LetterSpace]0[Trimer\[LetterSpace]import\[LetterSpace]to\[LetterSpace]nuc, cyt, pS2\[LetterSpace]pS2\[LetterSpace]S4\[LetterSpace]c[t]], reaction41 -> Function\[LetterSpace]for\[LetterSpace]reaction41\[LetterSpace]1\[LetterSpace]0[Trimer\[LetterSpace]import\[LetterSpace]to\[LetterSpace]nuc, cyt, pS2\[LetterSpace]pS2\[LetterSpace]pS2\[LetterSpace]c[t]], reaction42 -> k\[LetterSpace]Dephos*nuc*pS2\[LetterSpace]n[t], reaction43 -> nuc*Function\[LetterSpace]for\[LetterSpace]reaction43\[LetterSpace]0[index\[LetterSpace]trimer\[LetterSpace]dephos, k\[LetterSpace]Dephos, pS2\[LetterSpace]pS2\[LetterSpace]S4\[LetterSpace]n[t]], reaction44 -> cyt*Function\[LetterSpace]for\[LetterSpace]reaction44\[LetterSpace]3\[LetterSpace]0[S2\[LetterSpace]export\[LetterSpace]from\[LetterSpace]nuc, S2\[LetterSpace]import\[LetterSpace]to\[LetterSpace]nuc, S2\[LetterSpace]total, kdeg\[LetterSpace]S2], reaction45 -> cyt*Function\[LetterSpace]for\[LetterSpace]reaction45\[LetterSpace]4\[LetterSpace]0[S4\[LetterSpace]export\[LetterSpace]from\[LetterSpace]nuc, S4\[LetterSpace]import\[LetterSpace]to\[LetterSpace]nuc, S4\[LetterSpace]total, kdeg\[LetterSpace]S4], reaction46 -> cyt*Function\[LetterSpace]for\[LetterSpace]reaction46\[LetterSpace]4\[LetterSpace]0[R1\[LetterSpace]total, index\[LetterSpace]k\[LetterSpace]out\[LetterSpace]1\[LetterSpace]relative\[LetterSpace]speed, k\[LetterSpace]in\[LetterSpace]1, kdeg\[LetterSpace]R1], reaction47 -> cyt*Function\[LetterSpace]for\[LetterSpace]reaction47\[LetterSpace]4\[LetterSpace]0[R2\[LetterSpace]total, index\[LetterSpace]k\[LetterSpace]out\[LetterSpace]2\[LetterSpace]relative\[LetterSpace]speed, k\[LetterSpace]in\[LetterSpace]2, kdeg\[LetterSpace]R2], reaction5 -> cyt*Function\[LetterSpace]for\[LetterSpace]reaction5\[LetterSpace]0[Active\[LetterSpace]R2[t], index\[LetterSpace]kb\[LetterSpace]R2, kf\[LetterSpace]R2\[LetterSpace]activation], reaction50 -> nuc*Function\[LetterSpace]for\[LetterSpace]reaction50\[LetterSpace]\[LetterSpace]2\[LetterSpace]0[K\[LetterSpace]mran, hill\[LetterSpace]fact1, k\[LetterSpace]induced\[LetterSpace]S7\[LetterSpace]production, mRNA\[LetterSpace]prod, pS2\[LetterSpace]pS2\[LetterSpace]S4\[LetterSpace]n[t]], reaction51 -> Function\[LetterSpace]for\[LetterSpace]reaction51\[LetterSpace]1\[LetterSpace]0[Smad7mRNA1[t], export\[LetterSpace]cytoplasm, nuc], reaction52 -> cyt*Function\[LetterSpace]for\[LetterSpace]reaction52\[LetterSpace]2\[LetterSpace]0[Smad7mRNA[t], k\[LetterSpace]S7\[LetterSpace]protein], reaction53 -> cyt*kdeg\[LetterSpace]S2*S2\[LetterSpace]c[t], reaction54 -> kdeg\[LetterSpace]S2*nuc*S2\[LetterSpace]n[t], reaction55 -> kdeg\[LetterSpace]S2*nuc*pS2\[LetterSpace]n[t], reaction56 -> cyt*kdeg\[LetterSpace]S2*pS2\[LetterSpace]c[t], reaction57 -> cyt*kdeg\[LetterSpace]S4*S4\[LetterSpace]c[t], reaction58 -> kdeg\[LetterSpace]S4*nuc*S4\[LetterSpace]n[t], reaction59 -> cyt*kdeg\[LetterSpace]S2*pS2\[LetterSpace]pS2\[LetterSpace]S4\[LetterSpace]c[t], reaction6 -> cyt*Function\[LetterSpace]for\[LetterSpace]reaction6\[LetterSpace]0[Active\[LetterSpace]R2[t], index\[LetterSpace]kb\[LetterSpace]R2, k\[LetterSpace]medium, kf\[LetterSpace]R2\[LetterSpace]activation], reaction60 -> cyt*kdeg\[LetterSpace]S4*pS2\[LetterSpace]pS2\[LetterSpace]S4\[LetterSpace]c[t], reaction61 -> cyt*kdeg\[LetterSpace]S2*pS2\[LetterSpace]pS2\[LetterSpace]pS2\[LetterSpace]c[t], reaction62 -> kdeg\[LetterSpace]S2*nuc*pS2\[LetterSpace]pS2\[LetterSpace]S4\[LetterSpace]n[t], reaction63 -> kdeg\[LetterSpace]S4*nuc*pS2\[LetterSpace]pS2\[LetterSpace]S4\[LetterSpace]n[t], reaction64 -> kdeg\[LetterSpace]S2*nuc*pS2\[LetterSpace]pS2\[LetterSpace]pS2\[LetterSpace]n[t], reaction65 -> kmRNA1deg\[LetterSpace]S7*nuc*Smad7mRNA1[t], reaction66 -> cyt*kmRNAdeg\[LetterSpace]S7*Smad7mRNA[t], reaction67 -> cyt*kdeg\[LetterSpace]S7*S7[t], reaction68 -> cyt*WASH\[LetterSpace]LIGAND*TGFb[t], reaction7 -> cyt*kf\[LetterSpace]R1\[LetterSpace]activation*Active\[LetterSpace]R2[t]*TGFb\[LetterSpace]R1\[LetterSpace]surface[t], reaction8 -> cyt*Function\[LetterSpace]for\[LetterSpace]reaction8\[LetterSpace]0[Active\[LetterSpace]Rec[t], index\[LetterSpace]kb\[LetterSpace]R1, kf\[LetterSpace]R1\[LetterSpace]activation], reaction9 -> cyt*kdeg\[LetterSpace]R2*Active\[LetterSpace]Rec\[LetterSpace]endo[t] }; parameters = { K\[LetterSpace]mran -> 223.595257238238, R1\[LetterSpace]total -> 34.8728125404976, R2\[LetterSpace]total -> 34.9992000511296, S2\[LetterSpace]export\[LetterSpace]from\[LetterSpace]nuc -> 1.99869955250212, S2\[LetterSpace]import\[LetterSpace]to\[LetterSpace]nuc -> 0.371577202544786, S2\[LetterSpace]total -> 876.042139372642, S4\[LetterSpace]export\[LetterSpace]from\[LetterSpace]nuc -> 0.196810731388947, S4\[LetterSpace]import\[LetterSpace]to\[LetterSpace]nuc -> 0.0370885363056236, S4\[LetterSpace]total -> 629.893021850583, Trimer\[LetterSpace]import\[LetterSpace]to\[LetterSpace]nuc -> 0.14403262974308, WASH\[LetterSpace]LIGAND -> 0, effective -> 0.0, export\[LetterSpace]cytoplasm -> 0.030437091663097, hill\[LetterSpace]fact1 -> 3.98592596228747, index\[LetterSpace]active\[LetterSpace]Rec\[LetterSpace]internalize -> 0.537380811093942, index\[LetterSpace]induced\[LetterSpace]R2\[LetterSpace]deg -> 1.00037810941361, index\[LetterSpace]induced\[LetterSpace]ligand\[LetterSpace]deg -> 2.7210717377255, index\[LetterSpace]k\[LetterSpace]out\[LetterSpace]1\[LetterSpace]relative\[LetterSpace]speed -> 0.566651645025112, index\[LetterSpace]k\[LetterSpace]out\[LetterSpace]2\[LetterSpace]relative\[LetterSpace]speed -> 0.245785368672998, index\[LetterSpace]kb\[LetterSpace]R1 -> 1.61229612947783, index\[LetterSpace]kb\[LetterSpace]R2 -> 8.70467633794271, index\[LetterSpace]kb\[LetterSpace]homotrimer -> 0.0164056196749139, index\[LetterSpace]kf\[LetterSpace]homotrimer -> 4.48445616275042, index\[LetterSpace]seq\[LetterSpace]kb -> 0.000881183442123411, index\[LetterSpace]trimer\[LetterSpace]dephos -> 2.60999282198359, kS4\[LetterSpace]effective\[LetterSpace]2 -> 0.999999999999969, k\[LetterSpace]Dephos -> 0.139418263062769, k\[LetterSpace]S7\[LetterSpace]protein -> 0.218269773101254, k\[LetterSpace]disso\[LetterSpace]Active\[LetterSpace]Rec -> 0.00103714944572345, k\[LetterSpace]in\[LetterSpace]1 -> 0.20092069321314, k\[LetterSpace]in\[LetterSpace]2 -> 0.62580495280349, k\[LetterSpace]induced\[LetterSpace]S7\[LetterSpace]production -> 4.99901466408568, k\[LetterSpace]medium -> 2018.93290162616, k\[LetterSpace]phosphorylation -> 0.0701273900652988, kb\[LetterSpace]trimmer -> 1.60762398289129, kdeg\[LetterSpace]R1 -> 0.0586554820930934, kdeg\[LetterSpace]R2 -> 0.00100039445581987, kdeg\[LetterSpace]S2 -> 0.000514148278553222, kdeg\[LetterSpace]S4 -> 0.00480202730242853, kdeg\[LetterSpace]S7 -> 0.00102253743337089, kf\[LetterSpace]R1\[LetterSpace]activation -> 4.98547574132432, kf\[LetterSpace]R2\[LetterSpace]activation -> 4.95555330964476, kf\[LetterSpace]Seq\[LetterSpace]S7\[LetterSpace]Rec -> 0.882166671316411, kf\[LetterSpace]trimmer -> 4.81430089969474, kin\[LetterSpace]deg\[LetterSpace]Ligand -> 0.720198437381795, kmRNA1deg\[LetterSpace]S7 -> 0.0052188859785782, kmRNAdeg\[LetterSpace]S7 -> 0.0990155435421535, mRNA\[LetterSpace]prod -> 0.0130886858359441, offset\[LetterSpace]restimulation\[LetterSpace]2\[LetterSpace]5pM -> 0.0807, scale\[LetterSpace]restimulation\[LetterSpace]2\[LetterSpace]5pM -> 0.9826, cyt -> 2.0, nuc -> 1.0 }; assignments = { Function\[LetterSpace]for\[LetterSpace]reaction41\[LetterSpace]1\[LetterSpace]0[Trimer\[LetterSpace]import\[LetterSpace]to\[LetterSpace]nuc_,cyt_,pS2\[LetterSpace]pS2\[LetterSpace]pS2\[LetterSpace]c_] -> cyt*pS2\[LetterSpace]pS2\[LetterSpace]pS2\[LetterSpace]c*Trimer\[LetterSpace]import\[LetterSpace]to\[LetterSpace]nuc, Function\[LetterSpace]for\[LetterSpace]reaction20\[LetterSpace]3\[LetterSpace]0[TGFb\[LetterSpace]R1\[LetterSpace]endo_,index\[LetterSpace]k\[LetterSpace]out\[LetterSpace]1\[LetterSpace]relative\[LetterSpace]speed_,k\[LetterSpace]in\[LetterSpace]1_] -> index\[LetterSpace]k\[LetterSpace]out\[LetterSpace]1\[LetterSpace]relative\[LetterSpace]speed*k\[LetterSpace]in\[LetterSpace]1*TGFb\[LetterSpace]R1\[LetterSpace]endo, Function\[LetterSpace]for\[LetterSpace]reaction31\[LetterSpace]1\[LetterSpace]0[index\[LetterSpace]kf\[LetterSpace]homotrimer_,kf\[LetterSpace]trimmer_,pS2\[LetterSpace]n_] -> index\[LetterSpace]kf\[LetterSpace]homotrimer*kf\[LetterSpace]trimmer*pS2\[LetterSpace]n^3, Function\[LetterSpace]for\[LetterSpace]reaction39\[LetterSpace]4\[LetterSpace]0[S2\[LetterSpace]export\[LetterSpace]from\[LetterSpace]nuc_,nuc_,pS2\[LetterSpace]n_] -> nuc*pS2\[LetterSpace]n*S2\[LetterSpace]export\[LetterSpace]from\[LetterSpace]nuc, Function\[LetterSpace]for\[LetterSpace]reaction43\[LetterSpace]0[index\[LetterSpace]trimer\[LetterSpace]dephos_,k\[LetterSpace]Dephos_,pS2\[LetterSpace]pS2\[LetterSpace]S4\[LetterSpace]n_] -> index\[LetterSpace]trimer\[LetterSpace]dephos*k\[LetterSpace]Dephos*pS2\[LetterSpace]pS2\[LetterSpace]S4\[LetterSpace]n, Function\[LetterSpace]for\[LetterSpace]reaction47\[LetterSpace]4\[LetterSpace]0[R2\[LetterSpace]total_,index\[LetterSpace]k\[LetterSpace]out\[LetterSpace]2\[LetterSpace]relative\[LetterSpace]speed_,k\[LetterSpace]in\[LetterSpace]2_,kdeg\[LetterSpace]R2_] -> (kdeg\[LetterSpace]R2^2*k\[LetterSpace]in\[LetterSpace]2*R2\[LetterSpace]total)/(kdeg\[LetterSpace]R2^2 + kdeg\[LetterSpace]R2*k\[LetterSpace]in\[LetterSpace]2 + index\[LetterSpace]k\[LetterSpace]out\[LetterSpace]2\[LetterSpace]relative\[LetterSpace]speed*kdeg\[LetterSpace]R2*k\[LetterSpace]in\[LetterSpace]2), Function\[LetterSpace]for\[LetterSpace]reaction37\[LetterSpace]4\[LetterSpace]0[S4\[LetterSpace]export\[LetterSpace]from\[LetterSpace]nuc_,S4\[LetterSpace]n_,nuc_] -> nuc*S4\[LetterSpace]export\[LetterSpace]from\[LetterSpace]nuc*S4\[LetterSpace]n, Function\[LetterSpace]for\[LetterSpace]reaction30\[LetterSpace]0[index\[LetterSpace]kf\[LetterSpace]homotrimer_,kf\[LetterSpace]trimmer_,pS2\[LetterSpace]c_] -> index\[LetterSpace]kf\[LetterSpace]homotrimer*kf\[LetterSpace]trimmer*pS2\[LetterSpace]c^3, Function\[LetterSpace]for\[LetterSpace]reaction1\[LetterSpace]0[TGFb_,TGFb\[LetterSpace]R2\[LetterSpace]surface_,k\[LetterSpace]medium_,kf\[LetterSpace]R2\[LetterSpace]activation_] -> (kf\[LetterSpace]R2\[LetterSpace]activation*TGFb*TGFb\[LetterSpace]R2\[LetterSpace]surface)/k\[LetterSpace]medium, Function\[LetterSpace]for\[LetterSpace]reaction51\[LetterSpace]1\[LetterSpace]0[Smad7mRNA1_,export\[LetterSpace]cytoplasm_,nuc_] -> export\[LetterSpace]cytoplasm*nuc*Smad7mRNA1, Function\[LetterSpace]for\[LetterSpace]reaction2\[LetterSpace]0[TGFb_,TGFb\[LetterSpace]R2\[LetterSpace]surface_,kf\[LetterSpace]R2\[LetterSpace]activation_] -> kf\[LetterSpace]R2\[LetterSpace]activation*TGFb*TGFb\[LetterSpace]R2\[LetterSpace]surface, Function\[LetterSpace]for\[LetterSpace]reaction6\[LetterSpace]0[Active\[LetterSpace]R2_,index\[LetterSpace]kb\[LetterSpace]R2_,k\[LetterSpace]medium_,kf\[LetterSpace]R2\[LetterSpace]activation_] -> (Active\[LetterSpace]R2*index\[LetterSpace]kb\[LetterSpace]R2*kf\[LetterSpace]R2\[LetterSpace]activation)/k\[LetterSpace]medium, Function\[LetterSpace]for\[LetterSpace]reaction3\[LetterSpace]0[TGFb_,TGFb\[LetterSpace]R2\[LetterSpace]surface_,kf\[LetterSpace]R2\[LetterSpace]activation_] -> kf\[LetterSpace]R2\[LetterSpace]activation*TGFb*TGFb\[LetterSpace]R2\[LetterSpace]surface, Function\[LetterSpace]for\[LetterSpace]reaction22\[LetterSpace]3\[LetterSpace]0[Active\[LetterSpace]Rec_,index\[LetterSpace]active\[LetterSpace]Rec\[LetterSpace]internalize_,k\[LetterSpace]in\[LetterSpace]1_] -> Active\[LetterSpace]Rec*index\[LetterSpace]active\[LetterSpace]Rec\[LetterSpace]internalize*k\[LetterSpace]in\[LetterSpace]1, Function\[LetterSpace]for\[LetterSpace]reaction36\[LetterSpace]4\[LetterSpace]0[S4\[LetterSpace]c_,S4\[LetterSpace]import\[LetterSpace]to\[LetterSpace]nuc_,cyt_] -> cyt*S4\[LetterSpace]c*S4\[LetterSpace]import\[LetterSpace]to\[LetterSpace]nuc, Function\[LetterSpace]for\[LetterSpace]reaction34\[LetterSpace]3\[LetterSpace]0[S2\[LetterSpace]c_,S2\[LetterSpace]import\[LetterSpace]to\[LetterSpace]nuc_,cyt_] -> cyt*S2\[LetterSpace]c*S2\[LetterSpace]import\[LetterSpace]to\[LetterSpace]nuc, Function\[LetterSpace]for\[LetterSpace]reaction38\[LetterSpace]4\[LetterSpace]0[S2\[LetterSpace]import\[LetterSpace]to\[LetterSpace]nuc_,cyt_,pS2\[LetterSpace]c_] -> cyt*pS2\[LetterSpace]c*S2\[LetterSpace]import\[LetterSpace]to\[LetterSpace]nuc, Function\[LetterSpace]for\[LetterSpace]reaction52\[LetterSpace]2\[LetterSpace]0[Smad7mRNA_,k\[LetterSpace]S7\[LetterSpace]protein_] -> k\[LetterSpace]S7\[LetterSpace]protein*Smad7mRNA, Function\[LetterSpace]for\[LetterSpace]reaction21\[LetterSpace]3\[LetterSpace]0[TGFb\[LetterSpace]R2\[LetterSpace]endo_,index\[LetterSpace]k\[LetterSpace]out\[LetterSpace]2\[LetterSpace]relative\[LetterSpace]speed_,k\[LetterSpace]in\[LetterSpace]2_] -> index\[LetterSpace]k\[LetterSpace]out\[LetterSpace]2\[LetterSpace]relative\[LetterSpace]speed*k\[LetterSpace]in\[LetterSpace]2*TGFb\[LetterSpace]R2\[LetterSpace]endo, Function\[LetterSpace]for\[LetterSpace]reaction32\[LetterSpace]2\[LetterSpace]0[index\[LetterSpace]kb\[LetterSpace]homotrimer_,kb\[LetterSpace]trimmer_,pS2\[LetterSpace]pS2\[LetterSpace]pS2\[LetterSpace]n_] -> index\[LetterSpace]kb\[LetterSpace]homotrimer*kb\[LetterSpace]trimmer*pS2\[LetterSpace]pS2\[LetterSpace]pS2\[LetterSpace]n, Function\[LetterSpace]for\[LetterSpace]reaction4\[LetterSpace]0[Active\[LetterSpace]R2_,index\[LetterSpace]kb\[LetterSpace]R2_,kf\[LetterSpace]R2\[LetterSpace]activation_] -> Active\[LetterSpace]R2*index\[LetterSpace]kb\[LetterSpace]R2*kf\[LetterSpace]R2\[LetterSpace]activation, Function\[LetterSpace]for\[LetterSpace]reaction5\[LetterSpace]0[Active\[LetterSpace]R2_,index\[LetterSpace]kb\[LetterSpace]R2_,kf\[LetterSpace]R2\[LetterSpace]activation_] -> Active\[LetterSpace]R2*index\[LetterSpace]kb\[LetterSpace]R2*kf\[LetterSpace]R2\[LetterSpace]activation, Function\[LetterSpace]for\[LetterSpace]reaction25\[LetterSpace]\[LetterSpace]1\[LetterSpace]0[Active\[LetterSpace]Rec\[LetterSpace]endo_,S2\[LetterSpace]c_,k\[LetterSpace]phosphorylation_] -> Active\[LetterSpace]Rec\[LetterSpace]endo*k\[LetterSpace]phosphorylation*S2\[LetterSpace]c, Function\[LetterSpace]for\[LetterSpace]reaction50\[LetterSpace]\[LetterSpace]2\[LetterSpace]0[K\[LetterSpace]mran_,hill\[LetterSpace]fact1_,k\[LetterSpace]induced\[LetterSpace]S7\[LetterSpace]production_,mRNA\[LetterSpace]prod_,pS2\[LetterSpace]pS2\[LetterSpace]S4\[LetterSpace]n_] -> mRNA\[LetterSpace]prod + (k\[LetterSpace]induced\[LetterSpace]S7\[LetterSpace]production*pS2\[LetterSpace]pS2\[LetterSpace]S4\[LetterSpace]n^hill\[LetterSpace]fact1)/(K\[LetterSpace]mran^hill\[LetterSpace]fact1 + pS2\[LetterSpace]pS2\[LetterSpace]S4\[LetterSpace]n^hill\[LetterSpace]fact1), Function\[LetterSpace]for\[LetterSpace]reaction8\[LetterSpace]0[Active\[LetterSpace]Rec_,index\[LetterSpace]kb\[LetterSpace]R1_,kf\[LetterSpace]R1\[LetterSpace]activation_] -> Active\[LetterSpace]Rec*index\[LetterSpace]kb\[LetterSpace]R1*kf\[LetterSpace]R1\[LetterSpace]activation, Function\[LetterSpace]for\[LetterSpace]reaction15\[LetterSpace]0[Inactive\[LetterSpace]Rec_,index\[LetterSpace]seq\[LetterSpace]kb_,kf\[LetterSpace]Seq\[LetterSpace]S7\[LetterSpace]Rec_] -> Inactive\[LetterSpace]Rec*index\[LetterSpace]seq\[LetterSpace]kb*kf\[LetterSpace]Seq\[LetterSpace]S7\[LetterSpace]Rec, Function\[LetterSpace]for\[LetterSpace]reaction46\[LetterSpace]4\[LetterSpace]0[R1\[LetterSpace]total_,index\[LetterSpace]k\[LetterSpace]out\[LetterSpace]1\[LetterSpace]relative\[LetterSpace]speed_,k\[LetterSpace]in\[LetterSpace]1_,kdeg\[LetterSpace]R1_] -> (kdeg\[LetterSpace]R1^2*k\[LetterSpace]in\[LetterSpace]1*R1\[LetterSpace]total)/(kdeg\[LetterSpace]R1^2 + kdeg\[LetterSpace]R1*k\[LetterSpace]in\[LetterSpace]1 + index\[LetterSpace]k\[LetterSpace]out\[LetterSpace]1\[LetterSpace]relative\[LetterSpace]speed*kdeg\[LetterSpace]R1*k\[LetterSpace]in\[LetterSpace]1), Function\[LetterSpace]for\[LetterSpace]reaction40\[LetterSpace]4\[LetterSpace]0[Trimer\[LetterSpace]import\[LetterSpace]to\[LetterSpace]nuc_,cyt_,pS2\[LetterSpace]pS2\[LetterSpace]S4\[LetterSpace]c_] -> cyt*pS2\[LetterSpace]pS2\[LetterSpace]S4\[LetterSpace]c*Trimer\[LetterSpace]import\[LetterSpace]to\[LetterSpace]nuc, Function\[LetterSpace]for\[LetterSpace]reaction35\[LetterSpace]4\[LetterSpace]0[S2\[LetterSpace]export\[LetterSpace]from\[LetterSpace]nuc_,S2\[LetterSpace]n_,nuc_] -> nuc*S2\[LetterSpace]export\[LetterSpace]from\[LetterSpace]nuc*S2\[LetterSpace]n, Function\[LetterSpace]for\[LetterSpace]reaction33\[LetterSpace]3\[LetterSpace]0[index\[LetterSpace]kb\[LetterSpace]homotrimer_,kb\[LetterSpace]trimmer_,pS2\[LetterSpace]pS2\[LetterSpace]pS2\[LetterSpace]c_] -> index\[LetterSpace]kb\[LetterSpace]homotrimer*kb\[LetterSpace]trimmer*pS2\[LetterSpace]pS2\[LetterSpace]pS2\[LetterSpace]c, Function\[LetterSpace]for\[LetterSpace]reaction16\[LetterSpace]0[Inactive\[LetterSpace]Rec_,index\[LetterSpace]induced\[LetterSpace]ligand\[LetterSpace]deg_,kin\[LetterSpace]deg\[LetterSpace]Ligand_] -> Inactive\[LetterSpace]Rec*index\[LetterSpace]induced\[LetterSpace]ligand\[LetterSpace]deg*kin\[LetterSpace]deg\[LetterSpace]Ligand, Function\[LetterSpace]for\[LetterSpace]reaction17\[LetterSpace]0[Inactive\[LetterSpace]Rec_,index\[LetterSpace]induced\[LetterSpace]R2\[LetterSpace]deg_,kdeg\[LetterSpace]R2_] -> Inactive\[LetterSpace]Rec*index\[LetterSpace]induced\[LetterSpace]R2\[LetterSpace]deg*kdeg\[LetterSpace]R2, Function\[LetterSpace]for\[LetterSpace]reaction44\[LetterSpace]3\[LetterSpace]0[S2\[LetterSpace]export\[LetterSpace]from\[LetterSpace]nuc_,S2\[LetterSpace]import\[LetterSpace]to\[LetterSpace]nuc_,S2\[LetterSpace]total_,kdeg\[LetterSpace]S2_] -> ((kdeg\[LetterSpace]S2^2 + kdeg\[LetterSpace]S2*S2\[LetterSpace]export\[LetterSpace]from\[LetterSpace]nuc + kdeg\[LetterSpace]S2*S2\[LetterSpace]import\[LetterSpace]to\[LetterSpace]nuc)*S2\[LetterSpace]total)/(kdeg\[LetterSpace]S2 + S2\[LetterSpace]export\[LetterSpace]from\[LetterSpace]nuc + 2*S2\[LetterSpace]import\[LetterSpace]to\[LetterSpace]nuc), Function\[LetterSpace]for\[LetterSpace]reaction45\[LetterSpace]4\[LetterSpace]0[S4\[LetterSpace]export\[LetterSpace]from\[LetterSpace]nuc_,S4\[LetterSpace]import\[LetterSpace]to\[LetterSpace]nuc_,S4\[LetterSpace]total_,kdeg\[LetterSpace]S4_] -> ((kdeg\[LetterSpace]S4^2 + kdeg\[LetterSpace]S4*S4\[LetterSpace]export\[LetterSpace]from\[LetterSpace]nuc + kdeg\[LetterSpace]S4*S4\[LetterSpace]import\[LetterSpace]to\[LetterSpace]nuc)*S4\[LetterSpace]total)/(kdeg\[LetterSpace]S4 + S4\[LetterSpace]export\[LetterSpace]from\[LetterSpace]nuc + 2*S4\[LetterSpace]import\[LetterSpace]to\[LetterSpace]nuc), TGFb\[LetterSpace]Ligand\[LetterSpace]DOSE -> 100, NUC\[LetterSpace]CYT\[LetterSpace]SMAD2 -> offset\[LetterSpace]restimulation\[LetterSpace]2\[LetterSpace]5pM + (scale\[LetterSpace]restimulation\[LetterSpace]2\[LetterSpace]5pM*(pS2\[LetterSpace]n[t] + 3*pS2\[LetterSpace]pS2\[LetterSpace]pS2\[LetterSpace]n[t] + 2*pS2\[LetterSpace]pS2\[LetterSpace]S4\[LetterSpace]n[t] + S2\[LetterSpace]n[t]))/(pS2\[LetterSpace]c[t] + 3*pS2\[LetterSpace]pS2\[LetterSpace]pS2\[LetterSpace]c[t] + 2*pS2\[LetterSpace]pS2\[LetterSpace]S4\[LetterSpace]c[t] + S2\[LetterSpace]c[t]) }; events = { }; speciesAnnotations = { }; reactionAnnotations = { }; units = { {"time" -> "", "metabolite" -> "", "extent" -> ""} }; (* Time evolution *) odes = { Active\[LetterSpace]R2'[t] == 1.0*reaction3 +1.0*reaction8 -1.0*reaction4 -1.0*reaction7, Active\[LetterSpace]Rec'[t] == 1.0*reaction7 +1.0*reaction15 -1.0*reaction8 -1.0*reaction14 -1.0*reaction22, Active\[LetterSpace]Rec\[LetterSpace]endo'[t] == 1.0*reaction22 -1.0*reaction9 -1.0*reaction10 -1.0*reaction11 -1.0*reaction23, Inactive\[LetterSpace]Rec'[t] == 1.0*reaction14 -1.0*reaction15 -1.0*reaction16 -1.0*reaction17, S2\[LetterSpace]c'[t] == 1.0*reaction35 +1.0*reaction44 -1.0*reaction25 -1.0*reaction34 -1.0*reaction53, S2\[LetterSpace]n'[t] == 1.0*reaction34 +1.0*reaction42 +1.0*reaction43 -1.0*reaction35 -1.0*reaction54, S4\[LetterSpace]c'[t] == 1.0*reaction27 +1.0*reaction37 +1.0*reaction45 +1.0*reaction59 -1.0*reaction26 -1.0*reaction36 -1.0*reaction57, S4\[LetterSpace]n'[t] == 1.0*reaction29 +1.0*reaction36 +1.0*reaction43 +1.0*reaction62 -1.0*reaction28 -1.0*reaction37 -1.0*reaction58, S7'[t] == 1.0*reaction15 +1.0*reaction16 +1.0*reaction17 +1.0*reaction52 -1.0*reaction14 -1.0*reaction67, Smad7mRNA'[t] == 1.0*reaction51 -1.0*reaction66, Smad7mRNA1'[t] == 1.0*reaction50 -1.0*reaction51 -1.0*reaction65, TGFb'[t] == 1.0*reaction6 -1.0*reaction1 -1.0*reaction68, TGFb\[LetterSpace]In'[t] == 1.0*reaction9 +1.0*reaction10 +1.0*reaction17 +1.0*reaction23 -1.0*reaction24, TGFb\[LetterSpace]R1\[LetterSpace]endo'[t] == 1.0*reaction9 +1.0*reaction11 +1.0*reaction18 +1.0*reaction23 -1.0*reaction12 -1.0*reaction20, TGFb\[LetterSpace]R1\[LetterSpace]surface'[t] == 1.0*reaction8 +1.0*reaction16 +1.0*reaction17 +1.0*reaction20 +1.0*reaction46 -1.0*reaction7 -1.0*reaction18, TGFb\[LetterSpace]R2\[LetterSpace]endo'[t] == 1.0*reaction10 +1.0*reaction11 +1.0*reaction19 +1.0*reaction23 -1.0*reaction13 -1.0*reaction21, TGFb\[LetterSpace]R2\[LetterSpace]surface'[t] == 1.0*reaction5 +1.0*reaction16 +1.0*reaction21 +1.0*reaction47 -1.0*reaction2 -1.0*reaction19, pS2\[LetterSpace]c'[t] == 1.0*reaction25 +2.0*reaction27 +3.0*reaction33 +1.0*reaction39 +1.0*reaction59 +2.0*reaction60 +2.0*reaction61 -2.0*reaction26 -3.0*reaction30 -1.0*reaction38 -1.0*reaction56, pS2\[LetterSpace]n'[t] == 2.0*reaction29 +3.0*reaction32 +1.0*reaction38 +1.0*reaction43 +1.0*reaction62 +2.0*reaction63 +2.0*reaction64 -2.0*reaction28 -3.0*reaction31 -1.0*reaction39 -1.0*reaction42 -1.0*reaction55, pS2\[LetterSpace]pS2\[LetterSpace]S4\[LetterSpace]c'[t] == 1.0*reaction26 -1.0*reaction27 -1.0*reaction40 -1.0*reaction59 -1.0*reaction60, pS2\[LetterSpace]pS2\[LetterSpace]S4\[LetterSpace]n'[t] == 1.0*reaction28 +1.0*reaction40 -1.0*reaction29 -1.0*reaction43 -1.0*reaction62 -1.0*reaction63, pS2\[LetterSpace]pS2\[LetterSpace]pS2\[LetterSpace]c'[t] == 1.0*reaction30 -1.0*reaction33 -1.0*reaction41 -1.0*reaction61, pS2\[LetterSpace]pS2\[LetterSpace]pS2\[LetterSpace]n'[t] == 1.0*reaction31 +1.0*reaction41 -1.0*reaction32 -1.0*reaction64 }; 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]}]