// Created by libAntimony v2.8.0 model *Zi2011_TGFbeta_Pathway() // Compartments and Species: compartment default, Vmed, Vcyt, Vnuc; species TGF_beta_ex in Vmed, T1R_surf in Vcyt, T1R_endo in Vcyt, T2R_surf in Vcyt; species T2R_endo in Vcyt, LRC_surf in Vcyt, LRC_endo in Vcyt, Smad2c in Vcyt; species Smad2n in Vnuc, Smad4c in Vcyt, Smad4n in Vnuc, PSmad2c in Vcyt; species PSmad2_PSmad2_c in Vcyt, PSmad2_Smad4_c in Vcyt, PSmad2n in Vnuc; species PSmad2_PSmad2_n in Vnuc, PSmad2_Smad4_n in Vnuc, TGF_beta_endo in Vcyt; species TGF_beta_ns in Vmed, $AA in Vcyt, $empty_degraded in Vcyt; // Assignment Rules: Vmed := 2.000000e-003/(1.000000e+006*exp((ln(1.45)*time)/1440)); totalNumT1R := (T1R_surf + T1R_endo + LRC_surf + LRC_endo)*2.3*602; totalNumT2R := (T2R_surf + T2R_endo + LRC_surf + LRC_endo)*2.3*602; totalNumLRC := (LRC_surf + LRC_endo)*2.3*602; totalNumPSmad2 := (PSmad2c + PSmad2_PSmad2_c*2 + PSmad2_Smad4_c)*2.3*602 + (PSmad2n + PSmad2_PSmad2_n*2 + PSmad2_Smad4_n)*602; totalNuclearPSmad2 := PSmad2n + 2*PSmad2_PSmad2_n + PSmad2_Smad4_n; totalSmad2c := Smad2c + PSmad2c + 2*PSmad2_PSmad2_c + PSmad2_Smad4_c; totalSmad2n := Smad2n + PSmad2n + 2*PSmad2_PSmad2_n + PSmad2_Smad4_n; medium_TGF_beta_amount := TGF_beta_ex*1.000000e-009*Vmed*6.000000e+023; koff_ns := kon_ns*KD_ns; // Reactions: re1: $AA => T1R_surf; Vcyt*k_T1R; re2: T1R_surf => T1R_endo; Vcyt*ki*T1R_surf; re3: T1R_endo => T1R_surf; Vcyt*kr*T1R_endo; re4: T1R_endo => $empty_degraded; Vcyt*kdeg_T1R*T1R_endo; re5: $AA => T2R_surf; Vcyt*k_T2R; re6: T2R_surf => T2R_endo; Vcyt*ki*T2R_surf; re7: T2R_endo => T2R_surf; Vcyt*kr*T2R_endo; re8: T2R_endo => $empty_degraded; Vcyt*kdeg_T2R*T2R_endo; re9: TGF_beta_ex + T2R_surf + T1R_surf => LRC_surf; Vcyt*ka_LRC*TGF_beta_ex*T2R_surf*T1R_surf; re10: LRC_surf => LRC_endo; Vcyt*ki*LRC_surf; re11: LRC_endo => $empty_degraded; Vcyt*kdeg_LRC*LRC_endo; re12: LRC_endo => T1R_endo + T2R_endo + TGF_beta_endo; Vcyt*kdiss_LRC*LRC_endo; re13: TGF_beta_endo => $empty_degraded; Vcyt*kdeg_TGF_beta*TGF_beta_endo; re14: Smad2c => Smad2n; Vcyt*kimp_Smad2*Smad2c; re15: Smad2n => Smad2c; Vnuc*kexp_Smad2*Smad2n; re16: Smad4c => Smad4n; Vcyt*kimp_Smad4*Smad4c; re17: Smad4n => Smad4c; Vnuc*kexp_Smad4*Smad4n; re18: Smad2c => PSmad2c; Vcyt*kpho_Smad2*Smad2c*LRC_endo; re19: PSmad2c => PSmad2n; Vcyt*kimp_Smad2*PSmad2c; re20: PSmad2n => PSmad2c; Vnuc*kexp_Smad2*PSmad2n; re21: PSmad2c + Smad4c -> PSmad2_Smad4_c; Vcyt*(kon_Smads*PSmad2c*Smad4c - koff_Smads*PSmad2_Smad4_c); re22: PSmad2_Smad4_c => PSmad2_Smad4_n; Vcyt*kimp_Smads*PSmad2_Smad4_c; re23: PSmad2_Smad4_n -> PSmad2n + Smad4n; Vnuc*(koff_Smads*PSmad2_Smad4_n - kon_Smads*PSmad2n*Smad4n); re24: PSmad2n => Smad2n; Vnuc*kdepho_Smad2*PSmad2n; re25: 2PSmad2c -> PSmad2_PSmad2_c; Vcyt*(kon_Smads*PSmad2c^2 - koff_Smads*PSmad2_PSmad2_c); re26: PSmad2_PSmad2_c => PSmad2_PSmad2_n; Vcyt*kimp_Smads*PSmad2_PSmad2_c; re27: PSmad2_PSmad2_n -> 2PSmad2n; Vnuc*(koff_Smads*PSmad2_PSmad2_n - kon_Smads*PSmad2n^2); re28: LRC_surf => $empty_degraded; Vcyt*klid*LRC_surf*totalNuclearPSmad2; re29: TGF_beta_ex -> TGF_beta_ns; Vmed*(kon_ns*TGF_beta_ex - koff_ns*TGF_beta_ns); // Events: single_pulse_TGF_beta_washout: at 0 after stimulation_type == 2 && time == single_pulse_duration: TGF_beta_ex = 0; // Species initializations: TGF_beta_ex = 0.05; TGF_beta_ex has nM_per_volume; T1R_surf = (k_T1R*kdeg_T1R + k_T1R*kr)/(kdeg_T1R*ki); T1R_surf has nM_per_volume; T1R_endo = k_T1R/kdeg_T1R; T1R_endo has nM_per_volume; T2R_surf = (k_T2R*kdeg_T2R + k_T2R*kr)/(kdeg_T2R*ki); T2R_surf has nM_per_volume; T2R_endo = k_T2R/kdeg_T2R; T2R_endo has nM_per_volume; LRC_surf = 0; LRC_surf has nM_per_volume; LRC_endo = 0; LRC_endo has nM_per_volume; Smad2c = 60.6; Smad2c has nM_per_volume; Smad2n = 28.5; Smad2n has nM_per_volume; Smad4c = 50.8; Smad4c has nM_per_volume; Smad4n = 50.8; Smad4n has nM_per_volume; PSmad2c = 0; PSmad2c has nM_per_volume; PSmad2_PSmad2_c = 0; PSmad2_PSmad2_c has nM_per_volume; PSmad2_Smad4_c = 0; PSmad2_Smad4_c has nM_per_volume; PSmad2n = 0; PSmad2n has nM_per_volume; PSmad2_PSmad2_n = 0; PSmad2_PSmad2_n has nM_per_volume; PSmad2_Smad4_n = 0; PSmad2_Smad4_n has nM_per_volume; TGF_beta_endo = 0; TGF_beta_endo has nM_per_volume; TGF_beta_ns = 0; TGF_beta_ns has nM_per_volume; AA = 0; AA has nM_per_volume; empty_degraded = 0; empty_degraded has nM_per_volume; // Compartment initializations: default = 1; default has volume; Vmed has volume; Vcyt = 2.3e-012; Vcyt has volume; Vnuc = 1e-012; Vnuc has volume; // Variable initializations: k_T1R = 0.0167; k_T1R has nM_per_min; kdeg_T1R = 0.00256; kdeg_T1R has per_min; kr = 0.0333; kr has per_min; ki = 0.333; ki has per_min; k_T2R = 0.0190076; k_T2R has nM_per_min; kdeg_T2R = 0.0132; kdeg_T2R has per_min; stimulation_type = 1; stimulation_type has dimensionless; single_pulse_duration = 0.5; single_pulse_duration has min; totalNumT1R has molecules_per_cell; totalNumT2R has molecules_per_cell; totalNumLRC has molecules_per_cell; totalNumPSmad2 has molecules_per_cell; totalNuclearPSmad2 has nM; totalSmad2c has nM; totalSmad2n has nM; medium_TGF_beta_amount has molecules_per_cell; TGF_beta_dose_mol_per_cell = TGF_beta_ex*1.000000e-009*Vmed*6.000000e+023; TGF_beta_dose_mol_per_cell has molecules_per_cell; kdeg_LRC = 0.00256; kdeg_LRC has per_min; kdeg_TGF_beta = 0.347; kdeg_TGF_beta has per_min; klid = 0.0233678; klid has per_min; ka_LRC = 117.897; ka_LRC has third_order; kdiss_LRC = 0.0438111; kdiss_LRC has per_min; kimp_Smad2 = 0.156; kimp_Smad2 has per_min; kexp_Smad2 = 0.763; kexp_Smad2 has per_min; kimp_Smad4 = 0.156; kimp_Smad4 has per_min; kexp_Smad4 = 0.359; kexp_Smad4 has per_min; kpho_Smad2 = 0.0488268; kpho_Smad2 has second_order; kon_Smads = 0.198472; kon_Smads has second_order; koff_Smads = 1; koff_Smads has per_min; kimp_Smads = 0.889; kimp_Smads has per_min; kdepho_Smad2 = 0.394; kdepho_Smad2 has per_min; kon_ns = 0.0505413; kon_ns has per_min; koff_ns has per_min; KD_ns = 40.2257; KD_ns has dimensionless; // Other declarations: var Vmed, totalNumT1R, totalNumT2R, totalNumLRC, totalNumPSmad2, totalNuclearPSmad2; var totalSmad2c, totalSmad2n, medium_TGF_beta_amount, TGF_beta_dose_mol_per_cell; var koff_ns; const default, Vcyt, Vnuc, k_T1R, kdeg_T1R, kr, ki, k_T2R, kdeg_T2R, stimulation_type; const single_pulse_duration, kdeg_LRC, kdeg_TGF_beta, klid, ka_LRC, kdiss_LRC; const kimp_Smad2, kexp_Smad2, kimp_Smad4, kexp_Smad4, kpho_Smad2, kon_Smads; const koff_Smads, kimp_Smads, kdepho_Smad2, kon_ns, KD_ns; // Unit definitions: unit substance = 1e-9 mole; unit volume = litre; unit area = metre^2; unit length = metre; unit time_unit = 60 second; unit per_min = 1 / 60 second; unit nM_per_min = 1e-9 mole / 60 second; unit third_order = 1 / ((1e-9 mole)^2 * 60 second); unit second_order = 1 / (1e-9 mole * 60 second); unit min = 60 second; unit nM = 1e-9 mole; unit molecules_per_cell = dimensionless; unit nM_per_volume = 1e-9 mole / litre; // Display Names: time_unit is "min"; per_min is "per min"; nM_per_min is "nM per min"; third_order is "third order rate constant"; second_order is "second order rate constant"; min is "minute"; nM is "nanomolar"; molecules_per_cell is "molecules per cell"; Vmed is "Medium"; Vcyt is "Cytoplasm"; Vnuc is "Nucleus"; single_pulse_TGF_beta_washout is "TGF-beta washout in singel pulse stimulation"; re1 is "T1R production"; re2 is "T1R internalization to early endosome"; re3 is "T1R recycling from early endosome"; re4 is "T1R constitutive degradation"; re5 is "T2R production"; re6 is "T2R internalization to early endosome"; re7 is "T2R recycling from early endosome"; re8 is "T2R constitutive degradation"; re9 is "LRC activation"; re10 is "LRC internalization to early endosome"; re11 is "LRC constitutive degradation"; re12 is "dissociation of LRC in endosome"; re13 is "TGF-beta constitutive degradation"; re14 is "Smad2 nuclear import"; re15 is "Smad2 nuclear export"; re16 is "Smad4 nuclear import"; re17 is "Smad4 nuclear export"; re18 is "Smad2 phosphorylation"; re19 is "PSmad2 nuclear import"; re20 is "PSmad2 nuclear export"; re21 is "Smad2-Smad4 complex formation"; re22 is "Smad2-Smad4 nuclear import"; re23 is "Smad2-Smad4 dissociation"; re24 is "Smad2 dephosphorylation"; re25 is "PSmad2 dimer formation"; re26 is "PSmad2 dimer nuclear import"; re27 is "PSmad2 dimmer dissociation"; re28 is "negative feedback induced LRC degradation"; re29 is "non-specific binding of TGF-beta"; end