#strasen4



#reactions
reaction1:
 {1.0}TGFb = $pool
  cyt * Function_for_reaction1_0(TGFb, TGFb_R2_surface, k_medium, kf_R2_activation)
reaction10:
 {1.0}Active_Rec_endo = {1.0}TGFb_R2_endo + {1.0}TGFb_In
  cyt * kdeg_R1 * Active_Rec_endo
reaction11:
 {1.0}Active_Rec_endo = {1.0}TGFb_R1_endo + {1.0}TGFb_R2_endo
  cyt * kin_deg_Ligand * Active_Rec_endo
reaction12:
 {1.0}TGFb_R1_endo = $pool
  cyt * kdeg_R1 * TGFb_R1_endo
reaction13:
 {1.0}TGFb_R2_endo = $pool
  cyt * kdeg_R2 * TGFb_R2_endo
reaction14:
 {1.0}Active_Rec + {1.0}S7 = {1.0}Inactive_Rec
  cyt * kf_Seq_S7_Rec * Active_Rec * S7
reaction15:
 {1.0}Inactive_Rec = {1.0}Active_Rec + {1.0}S7
  cyt * Function_for_reaction15_0(Inactive_Rec, index_seq_kb, kf_Seq_S7_Rec)
reaction16:
 {1.0}Inactive_Rec = {1.0}TGFb_R1_surface + {1.0}TGFb_R2_surface + {1.0}S7
  cyt * Function_for_reaction16_0(Inactive_Rec, index_induced_ligand_deg, kin_deg_Ligand)
reaction17:
 {1.0}Inactive_Rec = {1.0}TGFb_R1_surface + {1.0}TGFb_In + {1.0}S7
  cyt * Function_for_reaction17_0(Inactive_Rec, index_induced_R2_deg, kdeg_R2)
reaction18:
 {1.0}TGFb_R1_surface = {1.0}TGFb_R1_endo
  cyt * k_in_1 * TGFb_R1_surface
reaction19:
 {1.0}TGFb_R2_surface = {1.0}TGFb_R2_endo
  cyt * k_in_2 * TGFb_R2_surface
reaction2:
 {1.0}TGFb_R2_surface = $pool
  cyt * Function_for_reaction2_0(TGFb, TGFb_R2_surface, kf_R2_activation)
reaction20:
 {1.0}TGFb_R1_endo = {1.0}TGFb_R1_surface
  cyt * Function_for_reaction20_3_0(TGFb_R1_endo, index_k_out_1_relative_speed, k_in_1)
reaction21:
 {1.0}TGFb_R2_endo = {1.0}TGFb_R2_surface
  cyt * Function_for_reaction21_3_0(TGFb_R2_endo, index_k_out_2_relative_speed, k_in_2)
reaction22:
 {1.0}Active_Rec = {1.0}Active_Rec_endo
  cyt * Function_for_reaction22_3_0(Active_Rec, index_active_Rec_internalize, k_in_1)
reaction23:
 {1.0}Active_Rec_endo = {1.0}TGFb_R1_endo + {1.0}TGFb_R2_endo + {1.0}TGFb_In
  cyt * k_disso_Active_Rec * Active_Rec_endo
reaction24:
 {1.0}TGFb_In = $pool
  cyt * kin_deg_Ligand * TGFb_In
reaction25:
 {1.0}S2_c = {1.0}pS2_c
  cyt * Function_for_reaction25__1_0(Active_Rec_endo, S2_c, k_phosphorylation)
reaction26:
 {2.0}pS2_c + {1.0}S4_c = {1.0}pS2_pS2_S4_c
  cyt * kf_trimmer * pow(pS2_c, 2) * S4_c
reaction27:
 {1.0}pS2_pS2_S4_c = {2.0}pS2_c + {1.0}S4_c
  cyt * kb_trimmer * pS2_pS2_S4_c
reaction28:
 {2.0}pS2_n + {1.0}S4_n = {1.0}pS2_pS2_S4_n
  nuc * kf_trimmer * pow(pS2_n, 2) * S4_n
reaction29:
 {1.0}pS2_pS2_S4_n = {2.0}pS2_n + {1.0}S4_n
  nuc * kb_trimmer * pS2_pS2_S4_n
reaction3:
 $pool = {1.0}Active_R2
  cyt * Function_for_reaction3_0(TGFb, TGFb_R2_surface, kf_R2_activation)
reaction30:
 {3.0}pS2_c = {1.0}pS2_pS2_pS2_c
  cyt * Function_for_reaction30_0(index_kf_homotrimer, kf_trimmer, pS2_c)
reaction31:
 {3.0}pS2_n = {1.0}pS2_pS2_pS2_n
  nuc * Function_for_reaction31_1_0(index_kf_homotrimer, kf_trimmer, pS2_n)
reaction32:
 {1.0}pS2_pS2_pS2_n = {3.0}pS2_n
  nuc * Function_for_reaction32_2_0(index_kb_homotrimer, kb_trimmer, pS2_pS2_pS2_n)
reaction33:
 {1.0}pS2_pS2_pS2_c = {3.0}pS2_c
  cyt * Function_for_reaction33_3_0(index_kb_homotrimer, kb_trimmer, pS2_pS2_pS2_c)
reaction34:
 {1.0}S2_c = {1.0}S2_n
  Function_for_reaction34_3_0(S2_c, S2_import_to_nuc, cyt)
reaction35:
 {1.0}S2_n = {1.0}S2_c
  Function_for_reaction35_4_0(S2_export_from_nuc, S2_n, nuc)
reaction36:
 {1.0}S4_c = {1.0}S4_n
  Function_for_reaction36_4_0(S4_c, S4_import_to_nuc, cyt)
reaction37:
 {1.0}S4_n = {1.0}S4_c
  Function_for_reaction37_4_0(S4_export_from_nuc, S4_n, nuc)
reaction38:
 {1.0}pS2_c = {1.0}pS2_n
  Function_for_reaction38_4_0(S2_import_to_nuc, cyt, pS2_c)
reaction39:
 {1.0}pS2_n = {1.0}pS2_c
  Function_for_reaction39_4_0(S2_export_from_nuc, nuc, pS2_n)
reaction4:
 {1.0}Active_R2 = $pool
  cyt * Function_for_reaction4_0(Active_R2, index_kb_R2, kf_R2_activation)
reaction40:
 {1.0}pS2_pS2_S4_c = {1.0}pS2_pS2_S4_n
  Function_for_reaction40_4_0(Trimer_import_to_nuc, cyt, pS2_pS2_S4_c)
reaction41:
 {1.0}pS2_pS2_pS2_c = {1.0}pS2_pS2_pS2_n
  Function_for_reaction41_1_0(Trimer_import_to_nuc, cyt, pS2_pS2_pS2_c)
reaction42:
 {1.0}pS2_n = {1.0}S2_n
  nuc * k_Dephos * pS2_n
reaction43:
 {1.0}pS2_pS2_S4_n = {1.0}pS2_n + {1.0}S2_n + {1.0}S4_n
  nuc * Function_for_reaction43_0(index_trimer_dephos, k_Dephos, pS2_pS2_S4_n)
reaction44:
 $pool = {1.0}S2_c
  cyt * Function_for_reaction44_3_0(S2_export_from_nuc, S2_import_to_nuc, S2_total, kdeg_S2)
reaction45:
 $pool = {1.0}S4_c
  cyt * Function_for_reaction45_4_0(S4_export_from_nuc, S4_import_to_nuc, S4_total, kdeg_S4)
reaction46:
 $pool = {1.0}TGFb_R1_surface
  cyt * Function_for_reaction46_4_0(R1_total, index_k_out_1_relative_speed, k_in_1, kdeg_R1)
reaction47:
 $pool = {1.0}TGFb_R2_surface
  cyt * Function_for_reaction47_4_0(R2_total, index_k_out_2_relative_speed, k_in_2, kdeg_R2)
reaction5:
 $pool = {1.0}TGFb_R2_surface
  cyt * Function_for_reaction5_0(Active_R2, index_kb_R2, kf_R2_activation)
reaction50:
 $pool = {1.0}Smad7mRNA1
  nuc * Function_for_reaction50__2_0(K_mran, hill_fact1, k_induced_S7_production, mRNA_prod, pS2_pS2_S4_n)
reaction51:
 {1.0}Smad7mRNA1 = {1.0}Smad7mRNA
  Function_for_reaction51_1_0(Smad7mRNA1, export_cytoplasm, nuc)
reaction52:
 $pool = {1.0}S7
  cyt * Function_for_reaction52_2_0(Smad7mRNA, k_S7_protein)
reaction53:
 {1.0}S2_c = $pool
  cyt * kdeg_S2 * S2_c
reaction54:
 {1.0}S2_n = $pool
  nuc * kdeg_S2 * S2_n
reaction55:
 {1.0}pS2_n = $pool
  nuc * kdeg_S2 * pS2_n
reaction56:
 {1.0}pS2_c = $pool
  cyt * kdeg_S2 * pS2_c
reaction57:
 {1.0}S4_c = $pool
  cyt * kdeg_S4 * S4_c
reaction58:
 {1.0}S4_n = $pool
  nuc * kdeg_S4 * S4_n
reaction59:
 {1.0}pS2_pS2_S4_c = {1.0}pS2_c + {1.0}S4_c
  cyt * kdeg_S2 * pS2_pS2_S4_c
reaction6:
 $pool = {1.0}TGFb
  cyt * Function_for_reaction6_0(Active_R2, index_kb_R2, k_medium, kf_R2_activation)
reaction60:
 {1.0}pS2_pS2_S4_c = {2.0}pS2_c
  cyt * kdeg_S4 * pS2_pS2_S4_c
reaction61:
 {1.0}pS2_pS2_pS2_c = {2.0}pS2_c
  cyt * kdeg_S2 * pS2_pS2_pS2_c
reaction62:
 {1.0}pS2_pS2_S4_n = {1.0}pS2_n + {1.0}S4_n
  nuc * kdeg_S2 * pS2_pS2_S4_n
reaction63:
 {1.0}pS2_pS2_S4_n = {2.0}pS2_n
  nuc * kdeg_S4 * pS2_pS2_S4_n
reaction64:
 {1.0}pS2_pS2_pS2_n = {2.0}pS2_n
  nuc * kdeg_S2 * pS2_pS2_pS2_n
reaction65:
 {1.0}Smad7mRNA1 = $pool
  nuc * kmRNA1deg_S7 * Smad7mRNA1
reaction66:
 {1.0}Smad7mRNA = $pool
  cyt * kmRNAdeg_S7 * Smad7mRNA
reaction67:
 {1.0}S7 = $pool
  cyt * kdeg_S7 * S7
reaction68:
 {1.0}TGFb = $pool
  cyt * WASH_LIGAND * TGFb
reaction7:
 {1.0}TGFb_R1_surface + {1.0}Active_R2 = {1.0}Active_Rec
  cyt * kf_R1_activation * TGFb_R1_surface * Active_R2
reaction8:
 {1.0}Active_Rec = {1.0}TGFb_R1_surface + {1.0}Active_R2
  cyt * Function_for_reaction8_0(Active_Rec, index_kb_R1, kf_R1_activation)
reaction9:
 {1.0}Active_Rec_endo = {1.0}TGFb_R1_endo + {1.0}TGFb_In
  cyt * kdeg_R2 * Active_Rec_endo


#parameters
K_mran = 223.595257238238
R1_total = 34.8728125404976
R2_total = 34.9992000511296
S2_export_from_nuc = 1.99869955250212
S2_import_to_nuc = 0.371577202544786
S2_total = 876.042139372642
S4_export_from_nuc = 0.196810731388947
S4_import_to_nuc = 0.0370885363056236
S4_total = 629.893021850583
Trimer_import_to_nuc = 0.14403262974308
WASH_LIGAND = 0
effective = 0.0
export_cytoplasm = 0.030437091663097
hill_fact1 = 3.98592596228747
index_active_Rec_internalize = 0.537380811093942
index_induced_R2_deg = 1.00037810941361
index_induced_ligand_deg = 2.7210717377255
index_k_out_1_relative_speed = 0.566651645025112
index_k_out_2_relative_speed = 0.245785368672998
index_kb_R1 = 1.61229612947783
index_kb_R2 = 8.70467633794271
index_kb_homotrimer = 0.0164056196749139
index_kf_homotrimer = 4.48445616275042
index_seq_kb = 0.000881183442123411
index_trimer_dephos = 2.60999282198359
kS4_effective_2 = 0.999999999999969
k_Dephos = 0.139418263062769
k_S7_protein = 0.218269773101254
k_disso_Active_Rec = 0.00103714944572345
k_in_1 = 0.20092069321314
k_in_2 = 0.62580495280349
k_induced_S7_production = 4.99901466408568
k_medium = 2018.93290162616
k_phosphorylation = 0.0701273900652988
kb_trimmer = 1.60762398289129
kdeg_R1 = 0.0586554820930934
kdeg_R2 = 0.00100039445581987
kdeg_S2 = 0.000514148278553222
kdeg_S4 = 0.00480202730242853
kdeg_S7 = 0.00102253743337089
kf_R1_activation = 4.98547574132432
kf_R2_activation = 4.95555330964476
kf_Seq_S7_Rec = 0.882166671316411
kf_trimmer = 4.81430089969474
kin_deg_Ligand = 0.720198437381795
kmRNA1deg_S7 = 0.0052188859785782
kmRNAdeg_S7 = 0.0990155435421535
mRNA_prod = 0.0130886858359441
offset_restimulation_2_5pM = 0.0807
scale_restimulation_2_5pM = 0.9826
cyt = 2.0
nuc = 1.0


#initial values
Active_R2 = 0.0
Active_Rec = 0.0
Active_Rec_endo = 0.0
Inactive_Rec = 0.0
S2_c = 638.6434569983527
S2_n = 237.39868237428928
S4_c = 460.47553390898076
S4_n = 169.41748794160233
S7 = 12.043365220732587
Smad7mRNA = 0.05642005114580563
Smad7mRNA1 = 0.3670825118716101
TGFb = 0.0
TGFb_In = 0.0
TGFb_R1_endo = 18.76309651441349
TGFb_R1_surface = 16.109716026084108
TGFb_R2_endo = 28.058081318683687
TGFb_R2_surface = 6.941118732445909
pS2_c = 0.0
pS2_n = 0.0
pS2_pS2_S4_c = 0.0
pS2_pS2_S4_n = 0.0
pS2_pS2_pS2_c = 0.0
pS2_pS2_pS2_n = 0.0


#assignment rules
!F TGFb_Ligand_DOSE = 100.0
!F NUC_CYT_SMAD2 = offset_restimulation_2_5pM + scale_restimulation_2_5pM * ((2.0 * pS2_pS2_S4_n + S2_n + pS2_n + 3.0 * pS2_pS2_pS2_n) / (2.0 * pS2_pS2_S4_c + S2_c + pS2_c + 3.0 * pS2_pS2_pS2_c))