# egfr_extended_hpp.bngl # Created by BioNetGen 2.2.4 version("2.2.4+") begin model begin parameters NA 6.0221e23 f 0.01 Vext 0.94e-12*f Vcyt 0.94e-12*f Vnuc 0.22e-12*f Egf_0 (680e-9*Vext)*NA Egfr_0 (100e-9*Vcyt)*NA PLCg_0 (105e-9*Vcyt)*NA Shc_0 (150e-9*Vcyt)*NA Grb2_0 ((58e-9+27e-9)*Vcyt)*NA Sos_0 ((7e-9+27e-9)*Vcyt)*NA kelim 5e-3 kp1 (0.003e9/Vext)/NA km1 0.06 kp2 (0.01e9/Vcyt)/NA km2 0.1 kp3 0.5 km3 4.505 kp5 (0.03e9/Vcyt)/NA km5 0.2 kp6 0.5 km6 0.025 kp7 (0.003e9/Vcyt)/NA km7 0.3 km8 0.01 kp9 (0.0015e9/Vcyt)/NA km9 0.05 kp10 (0.01e9/Vcyt)/NA km10 0.06 kp11 (0.00225e9/Vcyt)/NA km11 0.03 kp12 (0.0001e9/Vcyt)/NA km12 0.0015 kp13 (0.045e9/Vcyt)/NA km13 0.6 kp14 3.0 km14 0.03 kp15 (0.00045e9/Vcyt)/NA km15 0.3 km16 0.005 kp17 (0.003e9/Vcyt)/NA km17 0.1 kp18 (0.00045e9/Vcyt)/NA km18 0.3 kp19 (0.01e9/Vcyt)/NA km19 0.0214 kp20 (0.00012e9/Vcyt)/NA km20 0.12 kp21 (0.003e9/Vcyt)/NA km21 0.1 kp22 (0.03e9/Vcyt)/NA km22 0.064 kp23 (0.021e9/Vcyt)/NA km23 0.1 kp24 (0.009e9/Vcyt)/NA km24 0.0429 kp25 1.0 km25 0.03 GTP (180e-6*Vcyt)*NA GDP (18e-6*Vcyt)*NA GAP_0 (1e-9*Vcyt)*NA Ras_0 (0.40e-6*Vcyt)*NA Raf_0 (0.013e-6*Vcyt)*NA MEK_0 (1.4e-6*Vcyt)*NA ERK_0 (0.96e-6*Vcyt)*NA D 1000 khyd 3.5e-4 kdgdp 1.1e-4 kdgtp 2.5e-4 kagdp ((2.3e6*GDP)/NA)/Vcyt kagtp ((2.2e6*GTP)/NA)/Vcyt kcatgdp 3.9 kcatgtp 7.2e-1 Kmgdp (0.156e-6*Vcyt)*NA Kmgtp (0.156e-6*Vcyt)*NA kfgdp ((2.5e4*D)/NA)/Vcyt krgdp 1e-12 kfgtp ((2.5e4*D)/NA)/Vcyt krgtp (Kmgtp*kfgtp)-kcatgtp kcat_GAP 5.40 Km_GAP (0.23e-6*Vcyt)*NA kf_GAP ((1e5*D)/Vcyt)/NA kr_GAP (Km_GAP*kf_GAP)-kcat_GAP kp_f1 0.49e6 km_f1 0.049 kp_f2 0.65e6 km_f2 0.065 kp_f3 0.88e6 km_f3 0.088 Vm_f6 0.18 Vm_f5 0.22 k_f16 0.010 k_f17 0.014 kex_f7 0.61 kin_f7 0.046 kex_f10 0.54 kin_f10 0.040 kex_f9 0.018 kin_f9 0.0086 kex_f8 0.26 kin_f8 0.035 kex_f11 0.013 kin_f11 0.0070 InitialConc1 384933*f InitialConc2 32825*f InitialConc3 84912*f InitialConc4 3931*f InitialConc5 56608*f InitialConc6 59438*f InitialConc7 5057*f InitialConc8 529*f InitialConc9 391192*f InitialConc10 43988*f InitialConc11 15198*f InitialConc12 214883*f InitialConc13 9093*f InitialConc14 298315*f InitialConc15 30348*f InitialConc16 60758*f InitialConc17 12*f InitialConc18 46*f InitialConc19 12*f InitialConc20 47*f InitialConc21 37*f InitialConc22 812*f InitialConc23 38240*f InitialConc24 1489*f InitialConc25 24956*f InitialConc26 5465*f InitialConc27 1858*f InitialConc28 646*f InitialConc29 72077*f InitialConc30 23946*f rateLaw1 D*kp10 rateLaw2 D*kp11 rateLaw3 D*kp20 rateLaw4 D*kp24 rateLaw5 D*kp19 rateLaw6 kfgdp/D rateLaw7 kfgdp/D rateLaw8 kfgdp/D rateLaw9 kfgtp/D rateLaw10 kfgtp/D rateLaw11 kfgtp/D rateLaw12 (kp_f1/NA)/Vcyt rateLaw13 (kp_f2/NA)/Vcyt rateLaw14 (kp_f3/NA)/Vcyt rateLaw15 (kp_f3/NA)/Vcyt k_lump 100000 end parameters begin molecule types X0021() population X0009() population ERK(bind,phos~U~P,loc~cyt~nuc) X0001() population X0006() population X0023() population X0019() population Egf(r) X0014() population MEK(bind,phos~U~P,loc~cyt~nuc) X0002() population X0003() population GAP(ras) X0013() population Ras(nuc~U~GDP~GTP,raf,cat) X0005() population X0011() population X0016() population PLCg(a,b~0~P,c~0~I) X0010() population Sos(dom,ras) X0024() population X0012() population X0004() population Shc(PTB,Y317~Y~pY) X0007() population X0015() population Grb2(SH2,SH3) X0025() population X0022() population Raf(ras,bind,phos~P~U) X0018() population X0017() population Egfr(l,d,Y992~Y~pY,Y1068~Y~pY,Y1148~Y~pY) X0008() population X0020() population end molecule types begin observables Molecules Dimers Egfr(d!1).Egfr(d!1) Molecules RP Egfr(Y992~pY!?) Egfr(Y1068~pY!?) Egfr(Y1148~pY!?) Molecules Shc_Grb Shc(Y317~pY!1).Grb2(SH2!1) Molecules Shc_Grb_Sos Shc(Y317~pY!1).Grb2(SH2!1,SH3!2).Sos(dom!2) Molecules R_Grb2 Egfr(Y1068~pY!1).Grb2(SH2!1) Molecules R_Shc Egfr(Y1148~pY!1).Shc(PTB!1,Y317~Y) Molecules R_ShcP Egfr(Y1148~pY!1).Shc(PTB!1,Y317~pY!?) Molecules R_pY992 Egfr(Y992~pY!?) Molecules R_PLCg Egfr(Y992~pY!1).PLCg(a!1) Molecules ShcP Shc(Y317~pY!?) Molecules PLCgP PLCg(b~P,c~0) X0003() Molecules PLCgPI PLCg(b~P,c~I) X0004() Molecules Sos_mem Shc(PTB!+,Y317~pY!1).Grb2(SH2!1,SH3!2).Sos(dom!2) Egfr(Y1068~pY!1).Grb2(SH2!1,SH3!2).Sos(dom!2) Molecules Sos_cyt Shc(PTB,Y317~pY!1).Grb2(SH2!1,SH3!2).Sos(dom!2) Grb2(SH2,SH3!1).Sos(dom!1) Sos(dom) Molecules RasGDP Ras(nuc~GDP) X0007() X0009() Molecules RasGTP Ras(nuc~GTP) X0008() X0012() X0013() Molecules RafU Raf(phos~U!?) X0010() Molecules RafP Raf(phos~P!?) X0011() X0012() X0013() Molecules MEK_act MEK(phos~P!?) X0016() X0017() X0024() X0025() Molecules ERK_act ERK(phos~P!?) X0020() X0021() Molecules MEK_nuc MEK(loc~nuc) X0015() X0017() X0023() X0025() Molecules ERK_nuc ERK(loc~nuc) X0019() X0021() X0023() X0025() Molecules MEK_P_nuc MEK(phos~P!?,loc~nuc) X0017() X0025() Molecules ERK_P_nuc ERK(phos~P!?,loc~nuc) X0021() Molecules Egf_tot Egf() X0001() Molecules Egfr_tot Egfr() Molecules PLCg_tot PLCg() X0002() X0003() X0004() Molecules Shc_tot Shc() Molecules Grb2_tot Grb2() Molecules Sos_tot Sos() Molecules GAP_tot GAP() X0005() X0009() Molecules Ras_tot Ras() X0006() X0007() X0008() X0009() X0012() X0013() Molecules Raf_tot Raf() X0010() X0011() X0012() X0013() Molecules MEK_tot MEK() X0013() X0014() X0015() X0016() X0017() X0022() X0023() X0024() X0025() Molecules ERK_tot ERK() X0018() X0019() X0020() X0021() X0022() X0023() X0024() X0025() end observables begin species X0001() InitialConc1 Grb2(SH2,SH3) InitialConc2 Shc(PTB,Y317~Y) InitialConc3 Sos(dom,ras) InitialConc4 Egfr(Y1068~Y,Y1148~Y,Y992~Y,d,l) InitialConc5 X0002() InitialConc6 X0010() InitialConc7 X0005() InitialConc8 X0014() InitialConc9 X0018() InitialConc10 Grb2(SH2,SH3!1).Sos(dom!1,ras) InitialConc11 X0007() InitialConc12 X0008() InitialConc13 X0022() InitialConc14 X0015() InitialConc15 X0019() InitialConc16 Ras(cat!1,nuc~GDP,raf).Sos(dom,ras!1) InitialConc17 Grb2(SH2,SH3!1).Ras(cat!2,nuc~GDP,raf).Sos(dom!1,ras!2) InitialConc18 Ras(cat!1,nuc~GTP,raf).Sos(dom,ras!1) InitialConc19 Grb2(SH2,SH3!1).Ras(cat!2,nuc~GTP,raf).Sos(dom!1,ras!2) InitialConc20 GAP(ras!1).Ras(cat!1,nuc~GTP,raf) InitialConc21 X0012() InitialConc22 X0023() InitialConc23 X0013() InitialConc24 X0016() InitialConc25 X0024() InitialConc26 X0017() InitialConc27 X0025() InitialConc28 X0020() InitialConc29 X0021() InitialConc30 X0003() 0 X0004() 0 X0006() 0 X0009() 0 X0011() 0 end species begin reaction rules EGF_elim_v1: X0001() -> 0 kelim B1_v1: Egfr(d,l) + X0001() -> Egf(r!1).Egfr(d,l!1) kp1 B1_rev_v1: Egf(r!1).Egfr(d,l!1) -> Egfr(d,l) + X0001() km1 DeleteMolecules B2_v1: Egfr(d,l!+) + Egfr(d,l!+) -> Egfr(d!1,l!+).Egfr(d!1,l!+) kp2 B2_rev_v1: Egfr(d!1,l!+).Egfr(d!1,l!+) -> Egfr(d,l!+) + Egfr(d,l!+) km2 B3p_992_v1: Egfr(Y992~Y,d!+) -> Egfr(Y992~pY,d!+) kp3 B3p_1068_v1: Egfr(Y1068~Y,d!+) -> Egfr(Y1068~pY,d!+) kp3 B3p_1148_v1: Egfr(Y1148~Y,d!+) -> Egfr(Y1148~pY,d!+) kp3 B3m_992_v1: Egfr(Y992~pY) -> Egfr(Y992~Y) km3 B3m_1068_v1: Egfr(Y1068~pY) -> Egfr(Y1068~Y) km3 B3m_1148_v1: Egfr(Y1148~pY) -> Egfr(Y1148~Y) km3 B14p_v1: Egfr(Y1148~pY!1,d!+).Shc(PTB!1,Y317~Y) -> Egfr(Y1148~pY!1,d!+).Shc(PTB!1,Y317~pY) kp14 B14m_v1: Shc(PTB!+,Y317~pY) -> Shc(PTB!+,Y317~Y) km14 B6p_v1: Egfr(Y992~pY!1,d!+).PLCg(a!1,b~0) -> Egfr(Y992~pY!1,d!+).PLCg(a!1,b~P) kp6 B6m_v1: Egfr(Y992~pY!1).PLCg(a!1,b~P) -> Egfr(Y992~pY!1).PLCg(a!1,b~0) km6 B5_v1: Egfr(Y992~pY) + X0002() -> Egfr(Y992~pY!1).PLCg(a!1,b~0,c~0) kp5 B5_rev_v1: Egfr(Y992~pY!1).PLCg(a!1,b~0,c~0) -> Egfr(Y992~pY) + X0002() km5 DeleteMolecules B7_v1: Egfr(Y992~pY) + X0003() -> Egfr(Y992~pY!1).PLCg(a!1,b~P,c~0) kp7 B7_rev_v1: Egfr(Y992~pY!1).PLCg(a!1,b~P,c~0) -> Egfr(Y992~pY) + X0003() km7 DeleteMolecules B9_v1: Egfr(Y1068~pY) + Grb2(SH2,SH3) -> Egfr(Y1068~pY!1).Grb2(SH2!1,SH3) kp9 B9_rev_v1: Egfr(Y1068~pY!1).Grb2(SH2!1,SH3) -> Egfr(Y1068~pY) + Grb2(SH2,SH3) km9 B10_cyt_v1: Egfr(Y1068~pY!1).Grb2(SH2!1,SH3) + Sos(dom,ras) -> Egfr(Y1068~pY!1).Grb2(SH2!1,SH3!2).Sos(dom!2,ras) kp10 B10_cyt_rev_v1: Egfr(Y1068~pY!1).Grb2(SH2!1,SH3!2).Sos(dom!2,ras) -> Egfr(Y1068~pY!1).Grb2(SH2!1,SH3) + Sos(dom,ras) km10 B10_mem_v1: Egfr(Y1068~pY!1).Grb2(SH2!1,SH3) + Sos(dom,ras!+) -> Egfr(Y1068~pY!1).Grb2(SH2!1,SH3!2).Sos(dom!2,ras!+) rateLaw1 B10_mem_rev_v1: Egfr(Y1068~pY!1).Grb2(SH2!1,SH3!2).Sos(dom!2,ras!+) -> Egfr(Y1068~pY!1).Grb2(SH2!1,SH3) + Sos(dom,ras!+) km10 B11_cyt_v1: Egfr(Y1068~pY) + Grb2(SH2,SH3!1).Sos(dom!1,ras) -> Egfr(Y1068~pY!1).Grb2(SH2!1,SH3!2).Sos(dom!2,ras) kp11 B11_cyt_rev_v1: Egfr(Y1068~pY!1).Grb2(SH2!1,SH3!2).Sos(dom!2,ras) -> Egfr(Y1068~pY) + Grb2(SH2,SH3!1).Sos(dom!1,ras) km11 B11_mem_v1: Egfr(Y1068~pY) + Grb2(SH2,SH3!1).Sos(dom!1,ras!+) -> Egfr(Y1068~pY!1).Grb2(SH2!1,SH3!2).Sos(dom!2,ras!+) rateLaw2 B11_mem_rev_v1: Egfr(Y1068~pY!1).Grb2(SH2!1,SH3!2).Sos(dom!2,ras!+) -> Egfr(Y1068~pY) + Grb2(SH2,SH3!1).Sos(dom!1,ras!+) km11 B13_v1: Egfr(Y1148~pY) + Shc(PTB,Y317~Y) -> Egfr(Y1148~pY!1).Shc(PTB!1,Y317~Y) kp13 B13_rev_v1: Egfr(Y1148~pY!1).Shc(PTB!1,Y317~Y) -> Egfr(Y1148~pY) + Shc(PTB,Y317~Y) km13 B15_v1: Egfr(Y1148~pY) + Shc(PTB,Y317~pY) -> Egfr(Y1148~pY!1).Shc(PTB!1,Y317~pY) kp15 B15_rev_v1: Egfr(Y1148~pY!1).Shc(PTB!1,Y317~pY) -> Egfr(Y1148~pY) + Shc(PTB,Y317~pY) km15 B18_v1: Egfr(Y1148~pY) + Grb2(SH2!1,SH3).Shc(PTB,Y317~pY!1) -> Egfr(Y1148~pY!1).Grb2(SH2!2,SH3).Shc(PTB!1,Y317~pY!2) kp18 B18_rev_v1: Egfr(Y1148~pY!1).Grb2(SH2!2,SH3).Shc(PTB!1,Y317~pY!2) -> Egfr(Y1148~pY) + Grb2(SH2!1,SH3).Shc(PTB,Y317~pY!1) km18 B20_cyt_v1: Egfr(Y1148~pY) + Grb2(SH2!1,SH3!2).Shc(PTB,Y317~pY!1).Sos(dom!2,ras) -> Egfr(Y1148~pY!1).Grb2(SH2!2,SH3!3).Shc(PTB!1,Y317~pY!2).Sos(dom!3,ras) kp20 B20_cyt_rev_v1: Egfr(Y1148~pY!1).Grb2(SH2!2,SH3!3).Shc(PTB!1,Y317~pY!2).Sos(dom!3,ras) -> Egfr(Y1148~pY) + Grb2(SH2!1,SH3!2).Shc(PTB,Y317~pY!1).Sos(dom!2,ras) km20 B20_mem_v1: Egfr(Y1148~pY) + Grb2(SH2!1,SH3!2).Shc(PTB,Y317~pY!1).Sos(dom!2,ras!+) -> Egfr(Y1148~pY!1).Grb2(SH2!2,SH3!3).Shc(PTB!1,Y317~pY!2).Sos(dom!3,ras!+) rateLaw3 B20_mem_rev_v1: Egfr(Y1148~pY!1).Grb2(SH2!2,SH3!3).Shc(PTB!1,Y317~pY!2).Sos(dom!3,ras!+) -> Egfr(Y1148~pY) + Grb2(SH2!1,SH3!2).Shc(PTB,Y317~pY!1).Sos(dom!2,ras!+) km20 B17_v1: Egfr(Y1148~pY!1).Shc(PTB!1,Y317~pY) + Grb2(SH2,SH3) -> Egfr(Y1148~pY!1).Grb2(SH2!2,SH3).Shc(PTB!1,Y317~pY!2) kp17 B17_rev_v1: Egfr(Y1148~pY!1).Grb2(SH2!2,SH3).Shc(PTB!1,Y317~pY!2) -> Egfr(Y1148~pY!1).Shc(PTB!1,Y317~pY) + Grb2(SH2,SH3) km17 B24_cyt_v1: Egfr(Y1148~pY!1).Shc(PTB!1,Y317~pY) + Grb2(SH2,SH3!1).Sos(dom!1,ras) -> Egfr(Y1148~pY!1).Grb2(SH2!2,SH3!3).Shc(PTB!1,Y317~pY!2).Sos(dom!3,ras) kp24 B24_cyt_rev_v1: Egfr(Y1148~pY!1).Grb2(SH2!2,SH3!3).Shc(PTB!1,Y317~pY!2).Sos(dom!3,ras) -> Egfr(Y1148~pY!1).Shc(PTB!1,Y317~pY) + Grb2(SH2,SH3!1).Sos(dom!1,ras) km24 B24_mem_v1: Egfr(Y1148~pY!1).Shc(PTB!1,Y317~pY) + Grb2(SH2,SH3!1).Sos(dom!1,ras!+) -> Egfr(Y1148~pY!1).Grb2(SH2!2,SH3!3).Shc(PTB!1,Y317~pY!2).Sos(dom!3,ras!+) rateLaw4 B24_mem_rev_v1: Egfr(Y1148~pY!1).Grb2(SH2!2,SH3!3).Shc(PTB!1,Y317~pY!2).Sos(dom!3,ras!+) -> Egfr(Y1148~pY!1).Shc(PTB!1,Y317~pY) + Grb2(SH2,SH3!1).Sos(dom!1,ras!+) km24 B19_cyt_v1: Grb2(SH2!1,SH3).Shc(PTB!+,Y317~pY!1) + Sos(dom,ras) -> Grb2(SH2!1,SH3!2).Shc(PTB!+,Y317~pY!1).Sos(dom!2,ras) kp19 B19_cyt_rev_v1: Grb2(SH2!1,SH3!2).Shc(PTB!+,Y317~pY!1).Sos(dom!2,ras) -> Grb2(SH2!1,SH3).Shc(PTB!+,Y317~pY!1) + Sos(dom,ras) km19 B19_mem_v1: Grb2(SH2!1,SH3).Shc(PTB!+,Y317~pY!1) + Sos(dom,ras!+) -> Grb2(SH2!1,SH3!2).Shc(PTB!+,Y317~pY!1).Sos(dom!2,ras!+) rateLaw5 B19_mem_rev_v1: Grb2(SH2!1,SH3!2).Shc(PTB!+,Y317~pY!1).Sos(dom!2,ras!+) -> Grb2(SH2!1,SH3).Shc(PTB!+,Y317~pY!1) + Sos(dom,ras!+) km19 B21_v1: Shc(PTB,Y317~pY) + Grb2(SH2,SH3) -> Grb2(SH2!1,SH3).Shc(PTB,Y317~pY!1) kp21 B21_rev_v1: Grb2(SH2!1,SH3).Shc(PTB,Y317~pY!1) -> Shc(PTB,Y317~pY) + Grb2(SH2,SH3) km21 B23_v1: Shc(PTB,Y317~pY) + Grb2(SH2,SH3!1).Sos(dom!1) -> Grb2(SH2!1,SH3!2).Shc(PTB,Y317~pY!1).Sos(dom!2) kp23 B23_rev_v1: Grb2(SH2!1,SH3!2).Shc(PTB,Y317~pY!1).Sos(dom!2) -> Shc(PTB,Y317~pY) + Grb2(SH2,SH3!1).Sos(dom!1) km23 B16_v1: Shc(PTB,Y317~pY) -> Shc(PTB,Y317~Y) km16 B12_v1: Grb2(SH2,SH3) + Sos(dom) -> Grb2(SH2,SH3!1).Sos(dom!1) kp12 B12_rev_v1: Grb2(SH2,SH3!1).Sos(dom!1) -> Grb2(SH2,SH3) + Sos(dom) km12 B22_v1: Grb2(SH2!1,SH3).Shc(PTB,Y317~pY!1) + Sos(dom) -> Grb2(SH2!1,SH3!2).Shc(PTB,Y317~pY!1).Sos(dom!2) kp22 B22_rev_v1: Grb2(SH2!1,SH3!2).Shc(PTB,Y317~pY!1).Sos(dom!2) -> Grb2(SH2!1,SH3).Shc(PTB,Y317~pY!1) + Sos(dom) km22 B8_v1: X0003() -> X0002() km8 B25_v1: X0003() -> X0004() kp25 B25_rev_v1: X0004() -> X0003() km25 S1_v1: X0006() -> X0007() kagdp S1_rev_v1: X0007() -> X0006() kdgdp S2_v1: X0006() -> X0008() kagtp S2_rev_v1: X0008() -> X0006() kdgtp S3_v1: X0008() -> X0007() khyd S4_v1: Sos(dom,ras) + X0007() -> Ras(cat!1,nuc~GDP,raf).Sos(dom,ras!1) rateLaw6 S4_rev_v1: Ras(cat!1,nuc~GDP,raf).Sos(dom,ras!1) -> Sos(dom,ras) + X0007() krgdp DeleteMolecules S5_v1: Grb2(SH2,SH3!1).Sos(dom!1,ras) + X0007() -> Grb2(SH2,SH3!1).Ras(cat!2,nuc~GDP,raf).Sos(dom!1,ras!2) rateLaw7 S5_rev_v1: Grb2(SH2,SH3!1).Ras(cat!2,nuc~GDP,raf).Sos(dom!1,ras!2) -> Grb2(SH2,SH3!1).Sos(dom!1,ras) + X0007() krgdp DeleteMolecules S6_v1: Grb2(SH2!1,SH3!2).Shc(PTB,Y317~pY!1).Sos(dom!2,ras) + X0007() -> Grb2(SH2!1,SH3!2).Ras(cat!3,nuc~GDP,raf).Shc(PTB,Y317~pY!1).Sos(dom!2,ras!3) rateLaw8 S6_rev_v1: Grb2(SH2!1,SH3!2).Ras(cat!3,nuc~GDP,raf).Shc(PTB,Y317~pY!1).Sos(dom!2,ras!3) -> Grb2(SH2!1,SH3!2).Shc(PTB,Y317~pY!1).Sos(dom!2,ras) + X0007() krgdp DeleteMolecules S7_v1: Grb2(SH2!1,SH3!2).Shc(PTB!+,Y317~pY!1).Sos(dom!2,ras) + X0007() -> Grb2(SH2!1,SH3!2).Ras(cat!3,nuc~GDP,raf).Shc(PTB!+,Y317~pY!1).Sos(dom!2,ras!3) kfgdp S7_rev_v1: Grb2(SH2!1,SH3!2).Ras(cat!3,nuc~GDP,raf).Shc(PTB!+,Y317~pY!1).Sos(dom!2,ras!3) -> Grb2(SH2!1,SH3!2).Shc(PTB!+,Y317~pY!1).Sos(dom!2,ras) + X0007() krgdp DeleteMolecules S8_v1: Egfr(Y1068~pY!1).Grb2(SH2!1,SH3!2).Sos(dom!2,ras) + X0007() -> Egfr(Y1068~pY!1).Grb2(SH2!1,SH3!2).Ras(cat!3,nuc~GDP,raf).Sos(dom!2,ras!3) kfgdp S8_rev_v1: Egfr(Y1068~pY!1).Grb2(SH2!1,SH3!2).Ras(cat!3,nuc~GDP,raf).Sos(dom!2,ras!3) -> Egfr(Y1068~pY!1).Grb2(SH2!1,SH3!2).Sos(dom!2,ras) + X0007() krgdp DeleteMolecules S9_v1: Sos(dom,ras) + X0008() -> Ras(cat!1,nuc~GTP,raf).Sos(dom,ras!1) rateLaw9 S9_rev_v1: Ras(cat!1,nuc~GTP,raf).Sos(dom,ras!1) -> Sos(dom,ras) + X0008() krgtp DeleteMolecules S10_v1: Grb2(SH2,SH3!1).Sos(dom!1,ras) + X0008() -> Grb2(SH2,SH3!1).Ras(cat!2,nuc~GTP,raf).Sos(dom!1,ras!2) rateLaw10 S10_rev_v1: Grb2(SH2,SH3!1).Ras(cat!2,nuc~GTP,raf).Sos(dom!1,ras!2) -> Grb2(SH2,SH3!1).Sos(dom!1,ras) + X0008() krgtp DeleteMolecules S11_v1: Grb2(SH2!1,SH3!2).Shc(PTB,Y317~pY!1).Sos(dom!2,ras) + X0008() -> Grb2(SH2!1,SH3!2).Ras(cat!3,nuc~GTP,raf).Shc(PTB,Y317~pY!1).Sos(dom!2,ras!3) rateLaw11 S11_rev_v1: Grb2(SH2!1,SH3!2).Ras(cat!3,nuc~GTP,raf).Shc(PTB,Y317~pY!1).Sos(dom!2,ras!3) -> Grb2(SH2!1,SH3!2).Shc(PTB,Y317~pY!1).Sos(dom!2,ras) + X0008() krgtp DeleteMolecules S12_v1: Grb2(SH2!1,SH3!2).Shc(PTB!+,Y317~pY!1).Sos(dom!2,ras) + X0008() -> Grb2(SH2!1,SH3!2).Ras(cat!3,nuc~GTP,raf).Shc(PTB!+,Y317~pY!1).Sos(dom!2,ras!3) kfgtp S12_rev_v1: Grb2(SH2!1,SH3!2).Ras(cat!3,nuc~GTP,raf).Shc(PTB!+,Y317~pY!1).Sos(dom!2,ras!3) -> Grb2(SH2!1,SH3!2).Shc(PTB!+,Y317~pY!1).Sos(dom!2,ras) + X0008() krgtp DeleteMolecules S13_v1: Egfr(Y1068~pY!1).Grb2(SH2!1,SH3!2).Sos(dom!2,ras) + X0008() -> Egfr(Y1068~pY!1).Grb2(SH2!1,SH3!2).Ras(cat!3,nuc~GTP,raf).Sos(dom!2,ras!3) kfgtp S13_rev_v1: Egfr(Y1068~pY!1).Grb2(SH2!1,SH3!2).Ras(cat!3,nuc~GTP,raf).Sos(dom!2,ras!3) -> Egfr(Y1068~pY!1).Grb2(SH2!1,SH3!2).Sos(dom!2,ras) + X0008() krgtp DeleteMolecules S14_v1: Ras(cat!1,nuc~GDP,raf).Sos(ras!1) -> Ras(cat!1,nuc~GTP,raf).Sos(ras!1) kcatgdp S14_rev_v1: Ras(cat!1,nuc~GTP,raf).Sos(ras!1) -> Ras(cat!1,nuc~GDP,raf).Sos(ras!1) kcatgtp S15_v1: X0008() + X0005() -> GAP(ras!1).Ras(cat!1,nuc~GTP,raf) kf_GAP S15_rev_v1: GAP(ras!1).Ras(cat!1,nuc~GTP,raf) -> X0008() + X0005() kr_GAP S16_v1: GAP(ras!1).Ras(cat!1,nuc~GTP,raf) -> X0007() + X0005() kcat_GAP F1_v1: X0008() + X0010() -> X0012() rateLaw12 F1_rev_v1: X0012() -> X0008() + X0010() km_f1 F2_v1: Raf(bind,phos~P,ras!1).Ras(nuc~GTP,raf!1) + X0014() -> MEK(bind!1,loc~cyt,phos~U).Raf(bind!1,phos~P,ras!2).Ras(nuc~GTP,raf!2) rateLaw13 F2_v2: X0012() + X0014() -> X0013() rateLaw13 F2_rev_v1: MEK(bind!1,loc~cyt,phos~U).Raf(bind!1,phos~P,ras!2).Ras(nuc~GTP,raf!2) -> Raf(bind,phos~P,ras!1).Ras(nuc~GTP,raf!1) + X0014() km_f2 DeleteMolecules F2_rev_v2: X0013() -> X0012() + X0014() km_f2 F6_v1: MEK(bind!1,loc~cyt,phos~U).Raf(bind!1,phos~P,ras!2).Ras(nuc~GTP,raf!2) -> Raf(bind,phos~P,ras!1).Ras(nuc~GTP,raf!1) + X0016() Vm_f6 DeleteMolecules F6_v2: X0013() -> X0012() + X0016() Vm_f6 F3_v1: MEK(bind,loc~cyt) + X0018() -> ERK(bind!1,loc~cyt,phos~U).MEK(bind!1,loc~cyt) rateLaw14 F3_v2: X0014() + X0018() -> X0022() rateLaw14 F3_v3: X0016() + X0018() -> X0024() rateLaw14 F3_rev_v1: ERK(bind!1,loc~cyt,phos~U).MEK(bind!1,loc~cyt) -> MEK(bind,loc~cyt) + X0018() km_f3 DeleteMolecules F3_rev_v2: X0022() -> X0014() + X0018() km_f3 F3_rev_v3: X0024() -> X0016() + X0018() km_f3 F13_v1: MEK(bind,loc~nuc) + X0019() -> ERK(bind!1,loc~nuc,phos~U).MEK(bind!1,loc~nuc) rateLaw15 F13_v2: X0015() + X0019() -> X0023() rateLaw15 F13_v3: X0017() + X0019() -> X0025() rateLaw15 F13_rev_v1: ERK(bind!1,loc~nuc,phos~U).MEK(bind!1,loc~nuc) -> MEK(bind,loc~nuc) + X0019() km_f3 DeleteMolecules F13_rev_v2: X0023() -> X0015() + X0019() km_f3 F13_rev_v3: X0025() -> X0017() + X0019() km_f3 F5_v1: ERK(bind!1,phos~U).MEK(bind!1,phos~P) -> MEK(bind,phos~P) + ERK(bind,phos~P) Vm_f5 F5_v2: X0024() -> X0016() + X0020() Vm_f5 F5_v3: X0025() -> X0017() + X0021() Vm_f5 F7_v1: X0015() -> X0014() kex_f7 F7_rev_v1: X0014() -> X0015() kin_f7 F10_v1: X0017() -> X0016() kex_f10 F10_rev_v1: X0016() -> X0017() kin_f10 F8_v1: ERK(bind!1,loc~nuc).MEK(bind!1,loc~nuc) -> ERK(bind!1,loc~cyt).MEK(bind!1,loc~cyt) kex_f8 F8_v2: X0023() -> X0022() kex_f8 F8_v3: X0025() -> X0024() kex_f8 F8_rev_v1: ERK(bind!1,loc~cyt).MEK(bind!1,loc~cyt) -> ERK(bind!1,loc~nuc).MEK(bind!1,loc~nuc) kin_f8 F8_rev_v2: X0022() -> X0023() kin_f8 F8_rev_v3: X0024() -> X0025() kin_f8 F9_v1: X0019() -> X0018() kex_f9 F9_rev_v1: X0018() -> X0019() kin_f9 F11_v1: X0021() -> X0020() kex_f11 F11_rev_v1: X0020() -> X0021() kin_f11 F16_v1: MEK(bind,phos~P) -> MEK(bind,phos~U) k_f16 F16_v2: X0016() -> X0014() k_f16 F16_v3: X0017() -> X0015() k_f16 F17_v1: ERK(bind,phos~P) -> ERK(bind,phos~U) k_f17 F17_v2: X0020() -> X0018() k_f17 F17_v3: X0021() -> X0019() k_f17 MapRule0: Egf(r) -> X0001() k_lump MapRule1: PLCg(a,b~0,c~0) -> X0002() k_lump MapRule2: PLCg(a,b~P,c~0) -> X0003() k_lump MapRule3: PLCg(a,b~P,c~I) -> X0004() k_lump MapRule4: GAP(ras) -> X0005() k_lump MapRule5: Ras(cat,nuc~U,raf) -> X0006() k_lump MapRule6: Ras(cat,nuc~GDP,raf) -> X0007() k_lump MapRule7: Ras(cat,nuc~GTP,raf) -> X0008() k_lump MapRule8: GAP(ras!1).Ras(cat!1,nuc~GDP,raf) -> X0009() k_lump MapRule9: Raf(bind,phos~U,ras) -> X0010() k_lump MapRule10: Raf(bind,phos~P,ras) -> X0011() k_lump MapRule11: Raf(bind,phos~P,ras!1).Ras(cat,nuc~GTP,raf!1) -> X0012() k_lump MapRule12: MEK(bind!1,loc~cyt,phos~U).Raf(bind!1,phos~P,ras!2).Ras(cat,nuc~GTP,raf!2) -> X0013() k_lump MapRule13: MEK(bind,loc~cyt,phos~U) -> X0014() k_lump MapRule14: MEK(bind,loc~nuc,phos~U) -> X0015() k_lump MapRule15: MEK(bind,loc~cyt,phos~P) -> X0016() k_lump MapRule16: MEK(bind,loc~nuc,phos~P) -> X0017() k_lump MapRule17: ERK(bind,loc~cyt,phos~U) -> X0018() k_lump MapRule18: ERK(bind,loc~nuc,phos~U) -> X0019() k_lump MapRule19: ERK(bind,loc~cyt,phos~P) -> X0020() k_lump MapRule20: ERK(bind,loc~nuc,phos~P) -> X0021() k_lump MapRule21: ERK(bind!1,loc~cyt,phos~U).MEK(bind!1,loc~cyt,phos~U) -> X0022() k_lump MapRule22: ERK(bind!1,loc~nuc,phos~U).MEK(bind!1,loc~nuc,phos~U) -> X0023() k_lump MapRule23: ERK(bind!1,loc~cyt,phos~U).MEK(bind!1,loc~cyt,phos~P) -> X0024() k_lump MapRule24: ERK(bind!1,loc~nuc,phos~U).MEK(bind!1,loc~nuc,phos~P) -> X0025() k_lump end reaction rules end model ## model actions ## simulate_nf({ t_end=>2400, n_steps=>120 ,gml=>10000000, complex=>0 })