#mueller1



#reactions
reaction_1:
 $pool = {1.0}S10
  cell * Function_for_reaction_1_0(cell, ks_c4, tf)
reaction_10:
 {1.0}S2 = {1.0}S14
  Nucleus * Function_for_reaction_10_0(S2, cell, kdeg_rbbound)
reaction_11:
 {1.0}S1 = $pool
  Nucleus * Function_for_reaction_11_0(S1, S11, cell, kdeg_rbp21)
reaction_12:
 {1.0}S2 = {1.0}S14
  Nucleus * Function_for_reaction_12_0(S11, S2, cell, kdeg_rbp21)
reaction_13:
 $pool = {1.0}S14
  Nucleus * Function_for_reaction_13_0(S14, cell, ks_e2fe2f, ks_e2fmyc, tf)
reaction_14:
 {1.0}S2 = {1.0}S1
  Nucleus * Function_for_reaction_14_0(S2, cell, kdeg_e2fbound)
reaction_15:
 {1.0}S2 = {1.0}S1 + {1.0}S14
  Nucleus * Function_for_reaction_15_0(S2, cell, kd_rbe2f)
reaction_16:
 {1.0}S1 = {1.0}S15
  Nucleus * Function_for_reaction_16_0(Km_prb, S1, S24, cell, kcatp_rbc4, nrb)
reaction_17:
 {1.0}S2 = {1.0}S16
  Nucleus * Function_for_reaction_17_0(Km_prb, S2, S24, cell, kcatp_rbc4, nrb)
reaction_18:
 {1.0}S5 = {1.0}S17
  Nucleus * Function_for_reaction_18_0(S14, S18, S5, cell, k_dna)
reaction_19:
 {1.0}S10 = $pool
  cell * Function_for_reaction_19_0(S10, cell, gsk3b, kdeg_c4, kdeg_c4gsk3b)
reaction_2:
 $pool = {1.0}S4
  cell * Function_for_reaction_2_0(S14, S16, cell, ks_c2e2f, ks_c2myc, tf)
reaction_20:
 {1.0}S13 = $pool
  Nucleus * Function_for_reaction_20_0(S13, cell, gsk3b, kdeg_c2, kdeg_c2gsk3b)
reaction_21:
 {1.0}S13 = {1.0}S18
  Nucleus * Function_for_reaction_21_0(S13, cell, kp_c2cak)
reaction_22:
 {1.0}S10 + {1.0}S12 = {1.0}S19
  cell * Function_for_reaction_22_0(S10, S12, cell, kb_p21c4)
reaction_23:
 {1.0}S4 + {1.0}S12 = {1.0}S20
  cell * Function_for_reaction_23_0(S12, S4, cell, kb_p21c2)
reaction_24:
 {1.0}S11 + {1.0}S13 = {1.0}S3
  Nucleus * Function_for_reaction_24_0(S11, S13, cell, kb_p21c2)
reaction_25:
 {1.0}S12 = {1.0}S11
  Function_for_reaction_25_0(S12, Vratio, cell, kimport)
reaction_26:
 {1.0}S12 = $pool
  cell * Function_for_reaction_26_0(S12, Vratio, cell, kimport)
reaction_27:
 {1.0}S11 = $pool
  Nucleus * Function_for_reaction_27_0(S11, cell, erk, gsk3b, kdeg_p21erk, kdeg_p21gsk3b)
reaction_28:
 {1.0}S12 = $pool
  cell * Function_for_reaction_28_0(S12, cell, erk, gsk3b, kdeg_p21erk, kdeg_p21gsk3b)
reaction_29:
 {1.0}S15 = $pool
  Nucleus * Function_for_reaction_29_0(S15, cell, kdeg_rbfree)
reaction_3:
 {1.0}S3 = {1.0}S11
  Nucleus * Function_for_reaction_3_0(S3, cell, gsk3b, kdeg_c2, kdeg_c2gsk3b)
reaction_30:
 {1.0}S16 = {1.0}S14
  Nucleus * Function_for_reaction_30_0(S16, cell, kdeg_rbbound)
reaction_31:
 {1.0}S15 = $pool
  Nucleus * Function_for_reaction_31_0(S11, S15, cell, kdeg_rbp21)
reaction_32:
 {1.0}S16 = {1.0}S14
  Nucleus * Function_for_reaction_32_0(S11, S16, cell, kdeg_rbp21)
reaction_33:
 {1.0}S14 = $pool
  Nucleus * Function_for_reaction_33_0(S14, cell, kdeg_e2ffree)
reaction_34:
 {1.0}S16 = {1.0}S15
  Nucleus * Function_for_reaction_34_0(S16, cell, kdeg_e2fbound)
reaction_35:
 {1.0}S1 + {1.0}S14 = {1.0}S2
  Nucleus * Function_for_reaction_35_0(S1, S14, cell, kb_rbe2f)
reaction_36:
 {1.0}S14 + {1.0}S15 = {1.0}S16
  Nucleus * Function_for_reaction_36_0(S14, S15, cell, kb_rbpe2f)
reaction_37:
 {1.0}S16 = {1.0}S14 + {1.0}S15
  Nucleus * Function_for_reaction_37_0(S16, cell, kd_rbpe2f)
reaction_38:
 {1.0}S15 = {1.0}S21
  Nucleus * Function_for_reaction_38_0(Km_prb, S15, S18, cell, kcatp_rbc2, nrb)
reaction_39:
 {1.0}S16 = {1.0}S14 + {1.0}S21
  Nucleus * Function_for_reaction_39_0(Km_prb, S16, S18, cell, kcatp_rbc2, nrb)
reaction_4:
 {1.0}S4 = $pool
  cell * Function_for_reaction_4_0(S4, cell, gsk3b, kdeg_c2, kdeg_c2gsk3b)
reaction_40:
 {1.0}S15 = {1.0}S1
  Nucleus * Function_for_reaction_40_0(Km_dprb, S15, S18, cell, kcatdp_rbc4, kinh_pp1, nrb)
reaction_41:
 {1.0}S16 = {1.0}S2
  Nucleus * Function_for_reaction_41_0(Km_dprb, S16, S18, cell, kcatdp_rbc4, kinh_pp1, nrb)
reaction_42:
 {1.0}S17 = {1.0}S22
  Nucleus * Function_for_reaction_42_0(S17, cell, k_delay)
reaction_43:
 {1.0}S19 = {1.0}S12
  cell * Function_for_reaction_43_0(S19, cell, gsk3b, kdeg_c4, kdeg_c4gsk3b)
reaction_44:
 {1.0}S18 = $pool
  Nucleus * Function_for_reaction_44_0(S18, cell, gsk3b, kdeg_c2, kdeg_c2gsk3b)
reaction_45:
 {1.0}S20 = {1.0}S12
  cell * Function_for_reaction_45_0(S20, cell, gsk3b, kdeg_c2, kdeg_c2gsk3b)
reaction_46:
 {1.0}S18 = $pool
  Nucleus * Function_for_reaction_46_0(S18, cell, gsk3b, kdeg_c2c2gsk3b)
reaction_47:
 {1.0}S18 = {1.0}S13
  Nucleus * Function_for_reaction_47_0(S18, cell, kdp_c2cak)
reaction_48:
 {1.0}S19 = {1.0}S10 + {1.0}S12
  cell * Function_for_reaction_48_0(S19, cell, kd_p21c4)
reaction_49:
 {1.0}S11 + {1.0}S18 = {1.0}S23
  Nucleus * Function_for_reaction_49_0(S11, S18, cell, kb_p21c2)
reaction_5:
 $pool = {1.0}S12
  cell * Function_for_reaction_5_0(S14, cell, ks_p21e2f, ks_p21p53, tfp21)
reaction_50:
 {1.0}S20 = {1.0}S4 + {1.0}S12
  cell * Function_for_reaction_50_0(S20, cell, kd_p21c2)
reaction_51:
 {1.0}S19 = {1.0}S24
  Function_for_reaction_51_0(S19, Vratio, cell, kimport)
reaction_52:
 {1.0}S20 = {1.0}S3
  Function_for_reaction_52_0(S20, Vratio, cell, kimport)
reaction_53:
 {1.0}S19 = $pool
  cell * Function_for_reaction_53_0(S19, Vratio, cell, kimport)
reaction_54:
 {1.0}S20 = $pool
  cell * Function_for_reaction_54_0(S20, Vratio, cell, kimport)
reaction_55:
 {1.0}S21 = $pool
  Nucleus * Function_for_reaction_55_0(S21, cell, kdeg_rbfree)
reaction_56:
 {1.0}S21 = $pool
  Nucleus * Function_for_reaction_56_0(S11, S21, cell, kdeg_rbp21)
reaction_57:
 {1.0}S21 = {1.0}S15
  Nucleus * Function_for_reaction_57_0(Km_dprb, S18, S21, cell, kcatdp_rbc2, kinh_pp1, nrb)
reaction_58:
 {1.0}S22 = {1.0}S25
  Nucleus * Function_for_reaction_58_0(S22, cell, k_delay)
reaction_59:
 {1.0}S24 = $pool
  Nucleus * Function_for_reaction_59_0(S24, cell, kdeg_c4)
reaction_6:
 {1.0}S3 = {1.0}S11 + {1.0}S13
  Nucleus * Function_for_reaction_6_0(S3, cell, kd_p21c2)
reaction_60:
 {1.0}S23 = {1.0}S11
  Nucleus * Function_for_reaction_60_0(S23, cell, gsk3b, kdeg_c2, kdeg_c2gsk3b)
reaction_61:
 {1.0}S24 = {1.0}S11 + {1.0}S26
  Nucleus * Function_for_reaction_61_0(S24, cell, kd_p21c4)
reaction_62:
 {1.0}S23 = {1.0}S11 + {1.0}S18
  Nucleus * Function_for_reaction_62_0(S23, cell, kd_p21c2)
reaction_63:
 {1.0}S23 = {1.0}S18
  Nucleus * Function_for_reaction_63_0(S14, S18, S23, cell, erk, kdeg_p21c2skp2, kdeg_p21erkskp2, kdeg_p21skp2)
reaction_64:
 {1.0}S24 = {1.0}S26
  Nucleus * Function_for_reaction_64_0(S14, S18, S24, cell, erk, kdeg_p21c2skp2, kdeg_p21erkskp2, kdeg_p21skp2)
reaction_65:
 {1.0}S25 = {1.0}S27
  Nucleus * Function_for_reaction_65_0(S25, cell, k_delay)
reaction_66:
 {1.0}S26 = $pool
  Nucleus * Function_for_reaction_66_0(S26, cell, gsk3b, kdeg_c4, kdeg_c4gsk3b)
reaction_67:
 {1.0}S11 + {1.0}S26 = {1.0}S24
  Nucleus * Function_for_reaction_67_0(S11, S26, cell, kb_p21c4)
reaction_68:
 {1.0}S27 = {1.0}S28
  Nucleus * Function_for_reaction_68_0(S27, cell, k_delay)
reaction_69:
 {1.0}S28 = $pool
  Nucleus * Function_for_reaction_69_0(S28, cell, k_delay)
reaction_7:
 {1.0}S3 = {1.0}S13
  Nucleus * Function_for_reaction_7_0(S14, S18, S3, cell, erk, kdeg_p21c2skp2, kdeg_p21erkskp2, kdeg_p21skp2)
reaction_8:
 $pool = {1.0}S1
  Nucleus * Function_for_reaction_8_0(S14, cell, ks_rb, ks_rbe2f)
reaction_9:
 {1.0}S1 = $pool
  Nucleus * Function_for_reaction_9_0(S1, cell, kdeg_rbfree)


#parameters
Kd_p21c2 = 0.0100024233821379
Kd_p21c4 = 99.9965429570432
Kd_rb_e2f = 50.002528361226
Kd_rbp_e2f = 481.484530572552
Km_dprb = 0.118988383643671
Km_prb = 2.03458881189349
Vcyto = 12.67
Vnuc = 0.25
aakt = 0.53
aerk = 0.16
atf = 0.601288203846636
k_delay = 23.6658781343201
k_dna = 0.00949790539669408
kb_p21c2 = 997.938141166465
kb_p21c4 = 14.3083360067931
kb_rbe2f = 229.976400323907
kb_rbpe2f = 182.218452288549
kc2cak = 0.316993285134466
kcatdp_rbc2 = 0.00313841707547858
kcatdp_rbc4 = 2892.0219338341
kcatp_rbc2 = 7142308.07232621
kcatprbc4 = 2797.82326282727
kdeg_c2 = 0.225746618767114
kdeg_c2c2gsk3b = 5.58835572681068
kdeg_c2gsk3b = 1.55090179808215e-05
kdeg_c4 = 1.01433121526038
kdeg_c4gsk3b = 0.107637073030656
kdeg_e2fbound = 0.0999954023364359
kdeg_p21c2skp2 = 0.040108041739907
kdeg_p21erk = 0.736488746268804
kdeg_p21erkskp2 = 0.000282976267377082
kdeg_p21gsk3b = 0.00464010657330714
kdeg_p21skp2 = 0.750574831653576
kdeg_rbbound = 0.0889964132806627
kdeg_rbp21 = 0.863570809432207
kdege2fplus = 4.18153340918872e-05
kdegrbplus = 0.257763482477731
kdp_c2cak = 101.282119534273
ki = 0.0918326575000322
kinh_p21akt = 0.439662894183616
kinh_pp1 = 16634.9400020267
ks_c2e2f = 2.19944932286058
ks_c2myc = 0.157511710670132
ks_c4 = 14298.6715905912
ks_e2fe2f = 0.459601740303536
ks_e2fmyc = 2.49174531457788e-06
ks_p21e2f = 0.811617200647839
ks_p21p53 = 3.84136205729286e-06
ks_rb = 72.5245257602228
ks_rbe2f = 20.0129834334888
nakt = 1.0957
nerk = 1.14663416967514
nrb = 3.0
pakt = 0.0348
perk = 0.00857314138104046
scale_PhosRbS788 = 0.673907327042472
scale_PhosRbS800 = 0.82377467648995
scale_TotCDK2T160 = 2.728395741944
scale_TotE2F = 28.7418
scale_TotRb = 0.2605
scale_TotcycDCDK4 = 0.5651
scale_TotcycECDK2 = 0.1889
scale_Totp21 = 0.1728
scale_Totp21CDK2 = 0.339790715037712
Nucleus = 1.0
cell = 1.0


#initial values
S1 = 25.5914
S10 = 0.0
S11 = 0.0
S12 = 0.0
S13 = 0.0
S14 = 0.0
S15 = 0.0
S16 = 0.0
S17 = 0.0
S18 = 0.0
S19 = 0.0
S2 = 0.0601
S20 = 0.0
S21 = 0.0
S22 = 0.0
S23 = 0.0
S24 = 0.0
S25 = 0.0
S26 = 0.0
S27 = 0.0
S28 = 0.0
S3 = 6.2223
S4 = 0.415
S5 = 1.0


#assignment rules
!F kdeg_e2ffree = kdeg_e2fbound + kdege2fplus
!F kcatp_rbc4 = kcatprbc4 * (1.0 - inhc4d1)
!F kd_rbpe2f = kb_rbpe2f * Kd_rbp_e2f
!F kd_rbe2f = kb_rbe2f * Kd_rb_e2f
!F hgf = piecewise(0.0, lt(time, -1.0), piecewise(0.0, lt(time, 24.0), 1.0))
!F inhp53 = piecewise(0.0, lt(time, -1.0), piecewise(0.0, lt(time, 0.0), 0.0))
!F inherk = piecewise(0.0, lt(time, -1.0), piecewise(0.0, lt(time, 0.0), 0.0))
!F inhakt = piecewise(0.0, lt(time, -1.0), piecewise(0.0, lt(time, 0.0), 0.0))
!F inhc4d1 = piecewise(0.0, lt(time, -1.0), piecewise(0.0, lt(time, 0.0), 0.0))
!F ObsTotE2F_obs = (scale_TotE2F + scale_TotRb) * Vnuc * (S2 + S14 + S16) / (Vnuc + Vcyto)
!F ObsTotCDK2T160_obs = scale_TotCDK2T160 * Vnuc * (S18 + S23) / (Vnuc + Vcyto)
!F ObsTotCycDCDK4_obs = scale_TotcycDCDK4 * (Vnuc * S24 + Vcyto * S19) / (Vnuc + Vcyto)
!F ObsPhosRbS788_obs = scale_PhosRbS788 * Vnuc * (S15 + S16 + S21) / (Vnuc + Vcyto)
!F ObsPhosRbS800_obs = scale_PhosRbS800 * Vnuc * S21 / (Vnuc + Vcyto)
!F ObsDNAContent_obs = 2.0 - (S5 + S17 + S22 + S25 + S27 + S28)
!F Vratio = Vnuc / Vcyto
!F gsk3b = 1.0 - akt
!F tf = (1.0 - atf) * erk * (1.0 - gsk3b) + atf
!F kp_c2cak = kdp_c2cak + kc2cak
!F kd_p21c4 = Kd_p21c4 * kb_p21c4
!F kd_p21c2 = Kd_p21c2 * kb_p21c2
!F kdeg_rbfree = kdeg_rbbound + kdegrbplus
!F kimport = ki / (1.0 + kinh_p21akt * akt)
!F tfp21 = (1.0 - inhp53) * tf
!F akt = (1.0 - inhakt) * ((1.0 - aakt) * (pow(pakt, nakt) + 1.0) * pow(hgf, nakt) / (pow(hgf, nakt) + pow(pakt, nakt)) + aakt)
!F erk = (1.0 - inherk) * ((1.0 - aerk) * (pow(perk, nerk) + 1.0) * pow(hgf, nerk) / (pow(hgf, nerk) + pow(perk, nerk)) + aerk)
!F ObsTotRb_obs = scale_TotRb * Vnuc * (S1 + S2 + S15 + S16 + S21) / (Vnuc + Vcyto)
!F ObsTotP21_obs = scale_Totp21 * (Vnuc * (S3 + S11 + S23 + S24) + Vcyto * (S12 + S19 + S20)) / (Vnuc + Vcyto)
!F ObsTotCycECDK2_obs = scale_TotcycECDK2 * (Vnuc * (S3 + S13 + S18 + S23) + Vcyto * (S4 + S20)) / (Vnuc + Vcyto)
!F ObsCDK2P21_obs = scale_Totp21CDK2 * (Vnuc * (S3 + S23) + Vcyto * S20) / (Vnuc + Vcyto)