// Created by libAntimony v2.8.0 model *ErbB() // Compartments and Species: compartment membrane; species E1 in membrane, E2 in membrane, E3 in membrane, E4 in membrane; species E_E1 in membrane, H_E3 in membrane, H_E4 in membrane, E11 in membrane; species E12 in membrane, E23 in membrane, E34 in membrane, E24 in membrane; species E44 in membrane, E11P in membrane, E12P in membrane, E23P in membrane; species E34P in membrane, E24P in membrane, E44P in membrane, G in membrane; species S in membrane, I in membrane, R in membrane, O in membrane, A in membrane; species E11G in membrane, E11S in membrane, E11R in membrane, E12G in membrane; species E12S in membrane, E12R in membrane, E23G in membrane, E23S in membrane; species E23I in membrane, E23R in membrane, E34G in membrane, E34S in membrane; species E34I in membrane, E34R in membrane, E24G in membrane, E24S in membrane; species E24I in membrane, E24R in membrane, E44G in membrane, E44S in membrane; species E44I in membrane, E44R in membrane, SigG in membrane, SigS in membrane; species SigI in membrane, SigR in membrane, SigA in membrane, SigSP in membrane; species SigAP in membrane, SigG_O in membrane, SigG_A in membrane, SigSP_G in membrane; species SigAP_S in membrane, SigAP_I in membrane, SigAP_R in membrane, Empty in membrane; species P3_A in membrane, P2 in membrane, P3 in membrane, Akt in membrane; species RsD in membrane, RsT in membrane, SigRP in membrane, Raf in membrane; species Rafstar in membrane, MEK in membrane, MEKstar in membrane, ERK in membrane; species ERKstar in membrane, OP in membrane, AP in membrane, A_SigG_O in membrane; species SigA_G in membrane, SigA_G_O in membrane, SigO in membrane, E13 in membrane; species E14 in membrane, E13P in membrane, E14P in membrane, E13G in membrane; species E13S in membrane, E13I in membrane, E13R in membrane, E14G in membrane; species E14S in membrane, E14I in membrane, E14R in membrane, T in membrane; species E11T in membrane, E12T in membrane, E23T in membrane, E34T in membrane; species E24T in membrane, E44T in membrane, E13T in membrane, E14T in membrane; species SigT in membrane, E1_PT in membrane, E2_PT in membrane, E4_PT in membrane; species E_E1_PT in membrane, H_E4_PT in membrane, Aktstar in membrane, SigAP_T in membrane; species E in membrane, H in membrane, fint in membrane, pERK in membrane; species ERK_MEKstar in membrane, pERK_MEKstar in membrane, pERK_ERKpase in membrane; species ERKpase in membrane, ERKstar_ERKpase in membrane, $norm_Akt_star in membrane; species $norm_Erk_star in membrane; // Assignment Rules: norm_Akt_star := Aktstar/18.8; norm_Erk_star := (ERKstar + ERKstar_ERKpase)/589.5; // Reactions: EGF_Binding_to_ErbB1: E1 -> E_E1; membrane*(kon1*E*E1 - EGF_off*E_E1); HRG_Binding_to_ErbB3: E3 -> H_E3; membrane*(kon2*H*E3 - HRGoff_3*H_E3); HRG_Binding_to_ErbB4: E4 -> H_E4; membrane*(kon3*H*E4 - HRGoff_4*H_E4); ErbB1_Dimerization: E_E1 + E_E1 -> E11; membrane*(kon4*E_E1*E_E1 - koff4*E11); ErbB1ErbB2_Heterodimerization: E_E1 + E2 -> E12; membrane*(kon5*E_E1*E2 - koff5*E12); ErbB2ErbB3_Heterodimerization: H_E3 + E2 -> E23; membrane*(kon6*H_E3*E2 - koff6*E23); ErbB3ErbB4_Heterodimerization: H_E3 + H_E4 -> E34; membrane*(kon7*H_E3*H_E4 - koff7*E34); ErbB2ErbB4_Heterodimerization: H_E4 + E2 -> E24; kon8*H_E4*E2 - koff8*E24; ErbB4_Homodimerization: H_E4 + H_E4 -> E44; membrane*(kon9*H_E4*H_E4 - koff9*E44); Net_E11_Phosphorylation: E11 -> E11P; membrane*(kf10*E11 - (VmaxPY*E11P)/(KmPY + E11P) - kPTP10*SigT*E11P); Net_E12_Phosphorylation: E12 -> E12P; membrane*(kf11*E12 - (VmaxPY*E12P)/(KmPY + E12P) - kPTP11*SigT*E12P); Net_E23_Phosphorylation: E23 -> E23P; membrane*(kf12*E23 - (VmaxPY*E23P)/(KmPY + E23P) - kPTP12*SigT*E23P); Net_E34_Phosphorylation: E34 -> E34P; membrane*(kf13*E34 - (VmaxPY*E34P)/(KmPY + E34P) - kPTP13*SigT*E34P); Net_E24_Phosphorylation: E24 -> E24P; membrane*(kf14*E24 - (VmaxPY*E24P)/(KmPY + E24P) - kPTP14*SigT*E24P); Net_E44_Phosphorylation: E44 -> E44P; membrane*(kf15*E44 - (VmaxPY*E44P)/(KmPY + E44P) - kPTP15*SigT*E44P); Net_E11PGrb2_binding: E11P + G -> E11G + SigG; membrane*(4*kon16*E11P*G - koff16*(SigG/(SigG + SigG_A + SigG_O + A_SigG_O + eps))*E11G); Net_E11PShc_binding: E11P + S -> E11S + SigS; membrane*(8*kon17*E11P*S - koff17*(SigS/(SigS + SigSP + SigSP_G + eps))*E11S); Net_E11PRasGAP_binding: E11P + R -> E11R + SigR; membrane*(2*kon18*E11P*R - koff18*(SigR/(SigR + SigRP + eps))*E11R); Net_E12PGrb2_binding: E12P + G -> E12G + SigG; membrane*(3*kon19*E12P*G - koff19*(SigG/(SigG + SigG_A + SigG_O + A_SigG_O + eps))*E12G); Net_E12PShc_binding: E12P + S -> E12S + SigS; membrane*(6*kon20*E12P*S - koff20*(SigS/(SigS + SigSP + SigSP_G + eps))*E12S); Net_E12PRasGAP_binding: E12P + R -> E12R + SigR; membrane*(2*kon21*E12P*R - koff21*(SigR/(SigR + SigRP + eps))*E12R); Net_E23PGrb2_binding: E23P + G -> E23G + SigG; membrane*(3*kon22*E23P*G - koff22*(SigG/(SigG + SigG_A + SigG_O + A_SigG_O + eps))*E23G); Net_E23PShc_binding: E23P + S -> E23S + SigS; membrane*(3*kon23*E23P*S - koff23*(SigS/(SigS + SigSP + SigSP_G + eps))*E23S); Net_E23PPI3K_binding: E23P + I -> E23I + SigI; membrane*(3*kon24*E23P*I - koff24*E23I); Net_E23PRasGAP_binding: E23P + R -> E23R + SigR; membrane*(2*kon25*E23P*R - koff25*(SigR/(SigR + SigRP + eps))*E23R); Net_E34PGrb2_binding: E34P + G -> E34G + SigG; membrane*(4*kon26*E34P*G - koff26*(SigG/(SigG + SigG_A + SigG_O + A_SigG_O + eps))*E34G); Net_E34PShc_binding: E34P + S -> E34S + SigS; membrane*(3*kon27*E34P*S - koff27*(SigS/(SigS + SigSP + SigSP_G + eps))*E34S); Net_E34PPI3K_binding: E34P + I -> E34I + SigI; membrane*(4*kon28*E34P*I - koff28*E34I); Net_E34PRasGAP_binding: E34P + R -> E34R + SigR; membrane*(2*kon29*E34P*R - koff29*(SigR/(SigR + SigRP + eps))*E34R); Net_E24PGrb2_binding: E24P + G -> E24G + SigG; membrane*(3*kon30*E24P*G - koff30*(SigG/(SigG + SigG_A + SigG_O + A_SigG_O + eps))*E24G); Net_E24PShc_binding: E24P + S -> E24S + SigS; membrane*(4*kon31*E24P*S - koff31*(SigS/(SigS + SigSP + SigSP_G + eps))*E24S); Net_E24PPI3K_binding: E24P + I -> E24I + SigI; membrane*(1*kon32*E24P*I - koff32*E24I); Net_E24PRasGAP_binding: E24P + R -> E24R + SigR; membrane*(2*kon33*E24P*R - koff33*(SigR/(SigR + SigRP + eps))*E24R); Net_E44PRasGAP_binding_1: E44P + G -> E44G + SigG; membrane*(4*kon34*E44P*G - koff34*(SigG/(SigG + SigG_A + SigG_O + A_SigG_O + eps))*E44G); Net_E44PShc_binding: E44P + S -> E44S + SigS; membrane*(4*kon35*E44P*S - koff35*(SigS/(SigS + SigSP + SigSP_G + eps))*E44S); Net_E44PPI3K_binding: E44P + I -> E44I + SigI; membrane*(2*kon36*E44P*I - koff36*E44I); Net_E44PRasGAP_binding_2: E44P + R -> E44R + SigR; membrane*(2*kon37*E44P*R - koff37*(SigR/(SigR + SigRP + eps))*E44R); Net_Shc_Phosphorylation: SigS -> SigSP; membrane*(kf38*SigS*(E11P + E12P + E23P + E24P + E34P + E44P + E13P + E14P) - (VmaxPY*SigSP)/(KmPY + SigSP) - kPTP38*SigT*SigSP); Net_Gab1_Phosphorylation: SigA -> SigAP; membrane*(kf39*SigA*(E11P + E12P + E23P + E24P + E34P + E44P + E13P + E14P) - (VmaxPY*SigAP)/(KmPY + SigAP) - kPTP39*SigT*SigAP); Net_Grb2SOS_binding: SigG + O -> SigG_O + SigO; membrane*(kon40*SigG*O - koff40*SigG_O); Net_Grb2Gab1_binding: SigG + A -> SigG_A + SigA; membrane*(kon41*SigG*A - koff41*SigG_A*(SigA/(eps + SigA + SigAP + SigAP_S + SigAP_R + SigAP_I + SigAP_T))); Net_ShcGrb2_binding: SigSP + G -> SigSP_G + SigG; membrane*(kon42*SigSP*G - koff42*SigSP_G*(SigG/(SigG + SigG_A + SigG_O + A_SigG_O + eps))); Net_Gab1Shc_binding: SigAP + S -> SigAP_S + SigS; membrane*(3*kon43*SigAP*S - koff43*SigAP_S*(SigS/(SigS + SigSP + SigSP_G + eps))); Net_Gab1PI3K_binding: SigAP + I -> SigAP_I + SigI; membrane*(3*kon44*SigAP*I - koff44*SigAP_I); Net_Gab1RasGAP_binding: SigAP + R -> SigAP_R + SigR; membrane*(2*kon45*SigAP*R - koff45*SigAP_R*(SigR/(SigR + SigRP + eps))); Net_Gab1PIP3_binding: P3 + A -> P3_A + SigA; membrane*(kon46*P3*A - koff46*P3_A*(SigA/(eps + SigA + SigAP + SigAP_S + SigAP_R + SigAP_I + SigAP_T))); Net_Akt_Activation: Akt -> Aktstar; membrane*((kf47*P3*Akt)/(Kmf47 + Akt) - (Vmaxr47*Aktstar)/(Kmr47 + Aktstar)); Net_PIP3_Production: P2 -> P3; membrane*((kf48*(1 - fint*(E11P/(E11P + E12P + E23P + E24P + E34P + E44P + E13P + E14P + eps)))*SigI*P2)/(Kmf48 + P2) - (3*PTEN*P3)/(Kmr48 + P3)); Net_RasGTP_Production: RsD -> RsT; membrane*((kf49*SigO*RsD)/(Kmf49 + RsD) - (kr49*SigR*RsT)/(Kmr49 + RsT) - (kr49b*SigRP*RsT)/(Kmr49b + RsT) - kcon49*RsT); Net_RasGAP_Phosphorylation: SigR -> SigRP; membrane*(kf50*SigR*(E11P + E12P + E23P + E24P + E34P + E44P + E13P + E14P) - (VmaxPY*SigRP)/(KmPY + SigRP) - kPTP50*SigT*SigRP); Net_Raf_Activation: Raf -> Rafstar; membrane*((kf51*RsT*Raf)/(Kmf51 + Raf) - (Vmaxr51*Rafstar)/(Kmrb51 + Rafstar)); Net_MEK_Activation: MEK -> MEKstar; membrane*((kf52*Rafstar*MEK)/(Kmf52 + MEK) - (Vmaxr52*MEKstar)/(Kmr52 + MEKstar)); Net_SOS_ST_Phosphorylation: O -> OP; membrane*((kf54*O*ERKstar)/(Kmf54 + O) - (Vmaxr54*OP)/(Kmr54 + OP)); Net_Gab1_ST_Phosphorylation: A -> AP; membrane*((kf55*A*ERKstar)/(Kmf55 + A) - (Vmaxr55*AP)/(Kmr55 + AP)); Grb2_binding_to_P3_A: G + P3_A -> SigA_G; membrane*(kon57*P3_A*G - koff57*SigA_G); SOS_binding_to_SigAG: SigA_G + O -> SigA_G_O + SigO; membrane*(kon58*SigA_G*O - koff58*SigA_G_O); Gab1_binding_to_SigGO: SigG_O + A -> A_SigG_O + SigA; membrane*(kon59*SigG_O*A - koff59*A_SigG_O*(SigA/(eps + SigA + SigAP + SigAP_S + SigAP_R + SigAP_I + SigAP_T))); SOS_binding_to_SigGA: SigG_A + O -> A_SigG_O + SigO; membrane*(kon60*SigG_A*O - koff60*A_SigG_O); ErbB1ErbB3_Heterodimerization: H_E3 + E_E1 -> E13; membrane*(kon61*H_E3*E_E1 - koff61*E13); ErbB1ErbB4_Heterodimerization: H_E4 + E_E1 -> E14; membrane*(kon62*H_E4*E_E1 - koff62*E14); Net_E13_Phosphorylation: E13 -> E13P; membrane*(kf63*E13 - (VmaxPY*E13P)/(KmPY + E13P) - kPTP63*SigT*E13P); Net_E14_Phosphorylation: E14 -> E14P; membrane*(kf64*E14 - (VmaxPY*E14P)/(KmPY + E14P) - kPTP64*SigT*E14P); Net_E13Grb2_Binding: E13P + G -> E13G + SigG; membrane*(4*kon65*E13P*G - koff65*(SigG/(SigG + SigG_A + SigG_O + A_SigG_O + eps))*E13G); Net_E13Shc_Binding: E13P + S -> E13S + SigS; membrane*(5*kon66*E13P*S - koff66*(SigS/(SigS + SigSP + SigSP_G + eps))*E13S); Net_E13PI3K_Binding: E13P + I -> E13I + SigI; membrane*(3*kon67*E13P*I - koff67*E13I); Net_E13RasGAP_Binding: E13P + R -> E13R + SigR; membrane*(2*kon68*E13P*R - koff68*(SigR/(SigR + SigRP + eps))*E13R); Net_E14Grb2_Binding: E14P + G -> E14G + SigG; membrane*(4*kon69*E14P*G - koff69*(SigG/(SigG + SigG_A + SigG_O + A_SigG_O + eps))*E14G); Net_E14Shc_Binding: E14P + S -> E14S + SigS; membrane*(6*kon70*E14P*S - koff70*(SigS/(SigS + SigSP + SigSP_G + eps))*E14S); Net_E14PI3K_Binding: E14P + I -> E14I + SigI; membrane*(1*kon71*E14P*I - koff71*E14I); Net_E14RasGAP_Binding: E14P + R -> E14R + SigR; membrane*(2*kon72*E14P*R - koff72*(SigR/(SigR + SigRP + eps))*E14R); Net_E11PTP1B_Binding: E11P + T -> E11T + SigT; membrane*(4*kon73*E11P*T - koff73*E11T); Net_E12PTP1B_Binding: E12P + T -> E12T + SigT; membrane*(3*kon74*E12P*T - koff74*E12T); Net_E23PTP1B_Binding: E23P + T -> E23T + SigT; membrane*(2*kon75*E23P*T - koff75*E23T); Net_E34PTP1B_Binding: E34P + T -> E34T + SigT; membrane*(2*kon76*E34P*T - koff76*E34T); Net_E24PTP1B_Binding: E24P + T -> E24T + SigT; membrane*(2*kon77*E24P*T - koff77*E24T); Net_E44PTP1B_Binding: E44P + T -> E44T + SigT; membrane*(2*kon78*E44P*T - koff78*E44T); Net_E13PTP1B_Binding: E13P + T -> E13T + SigT; membrane*(3*kon79*E13P*T - koff79*E13T); Net_E14PTP1B_Binding: E14P + T -> E14T + SigT; membrane*(3*kon80*E14P*T - koff80*E14T); Net_E1_ST_Phosphorylation: E1 -> E1_PT; membrane*((kf81*E1*ERKstar)/(Kmf81 + E1) - (Vmaxr81*E1_PT)/(Kmr81 + E1_PT)); Net_E2_ST_Phosphorylation: E2 -> E2_PT; membrane*((kf82*E2*ERKstar)/(Kmf82 + E2) - (Vmaxr82*E2_PT)/(Kmr82 + E2_PT)); Net_E4_ST_Phosphorylation: E4 -> E4_PT; membrane*((kf83*E4*ERKstar)/(Kmf83 + E4) - (Vmaxr83*E4_PT)/(Kmr83 + E4_PT)); Net_E_E1_ST_Phosphorylation: E_E1 -> E_E1_PT; membrane*((kf84*E_E1*ERKstar)/(Kmf84 + E_E1) - (Vmaxr84*E_E1_PT)/(Kmr84 + E_E1_PT)); Net_H_E4_ST_Phosphorylation: H_E4 -> H_E4_PT; membrane*((kf85*H_E4*ERKstar)/(Kmf85 + H_E4) - (Vmaxr85*H_E4_PT)/(Kmr85 + H_E4_PT)); EGF_binding_to_E1PT: E1_PT -> E_E1_PT; membrane*(kon86*E*E1_PT - EGF_off*E_E1_PT); HRG_binding_to_E4PT: E4_PT -> H_E4_PT; membrane*(kon87*H*E4_PT - HRGoff_4*H_E4_PT); PTP1B_binding_to_SigAP: SigAP + T -> SigAP_T + SigT; membrane*(2*kon88*SigAP*T - koff88*SigAP_T); E11P_Degradation: E11P => Empty; membrane*kdeg*E11P; E11G_Degradation: E11G + SigG => G; membrane*kdeg*E11G; E11S_Degradation: E11S + SigS => S; membrane*kdeg*E11S; E11R_Degradation: E11R + SigR => R; membrane*kdeg*E11R; E11T_Degradation: E11T + SigT => T; membrane*kdeg*E11T; mwbbde76d1_155c_4264_8447_4457527547cb: Empty => fint; membrane*a98*(-fint + b98); EGF_in_EC_compartment: E -> Empty; membrane*(((kon1*E*E1 - EGF_off*E_E1 + kon86*E*E1_PT) - EGF_off*E_E1_PT)/VeVc); HRG_in_EC_compartment: H -> Empty; membrane*((((kon87*H*E4_PT - HRGoff_4*H_E4_PT + kon2*H*E3) - HRGoff_3*H_E3 + kon3*H*E4) - HRGoff_4*H_E4)/VeVc); ERK_binding_to_MEKstar_1: ERK + MEKstar -> ERK_MEKstar; membrane*(kon89*ERK*MEKstar - koff89*ERK_MEKstar); pERK_production: ERK_MEKstar => pERK + MEKstar; membrane*kcat90*ERK_MEKstar; ERK_binding_to_MEKstar_2: pERK + MEKstar -> pERK_MEKstar; membrane*(kon91*pERK*MEKstar - koff91*pERK_MEKstar); ERKstar_production: pERK_MEKstar => ERKstar + MEKstar; membrane*kcat92*pERK_MEKstar; ERKstar_binding_to_Phosphatase: ERKstar + ERKpase -> ERKstar_ERKpase; membrane*(kon93*ERKstar*ERKpase - koff93*ERKstar_ERKpase); ERKstar_dephosphorylation: ERKstar_ERKpase => pERK + ERKpase; membrane*kcat94*ERKstar_ERKpase; pERK_binding_to_Phosphatase: pERK + ERKpase -> pERK_ERKpase; membrane*(kon95*pERK*ERKpase - koff95*pERK_ERKpase); pERK_dephosphorylation: pERK_ERKpase => ERK + ERKpase; membrane*kcat96*pERK_ERKpase; // Species initializations: E1 = 274/membrane; E2 = 158/membrane; E3 = 294/membrane; E4 = 399/membrane; E_E1 = 0; H_E3 = 0; H_E4 = 0; E11 = 0; E12 = 0; E23 = 0; E34 = 0; E24 = 0; E44 = 0; E11P = 0; E12P = 0; E23P = 0; E34P = 0; E24P = 0; E44P = 0; G = 82.4/membrane; S = 11.5/membrane; I = 46.4/membrane; R = 93.6/membrane; O = 82.3/membrane; A = 43.1/membrane; E11G = 0; E11S = 0; E11R = 0; E12G = 0; E12S = 0; E12R = 0; E23G = 0; E23S = 0; E23I = 0; E23R = 0; E34G = 0; E34S = 0; E34I = 0; E34R = 0; E24G = 0; E24S = 0; E24I = 0; E24R = 0; E44G = 0; E44S = 0; E44I = 0; E44R = 0; SigG = 0; SigS = 0; SigI = 0; SigR = 0; SigA = 0; SigSP = 0; SigAP = 0; SigG_O = 0; SigG_A = 0; SigSP_G = 0; SigAP_S = 0; SigAP_I = 0; SigAP_R = 0; Empty = 0; P3_A = 0; P2 = 197/membrane; P3 = 0; Akt = 444/membrane; RsD = 95.7/membrane; RsT = 0; SigRP = 0; Raf = 743/membrane; Rafstar = 0; MEK = 772/membrane; MEKstar = 0; ERK = 750/membrane; ERKstar = 0; OP = 0; AP = 0; A_SigG_O = 0; SigA_G = 0; SigA_G_O = 0; SigO = 0; E13 = 0; E14 = 0; E13P = 0; E14P = 0; E13G = 0; E13S = 0; E13I = 0; E13R = 0; E14G = 0; E14S = 0; E14I = 0; E14R = 0; T = 500/membrane; E11T = 0; E12T = 0; E23T = 0; E34T = 0; E24T = 0; E44T = 0; E13T = 0; E14T = 0; SigT = 0; E1_PT = 0; E2_PT = 0; E4_PT = 0; E_E1_PT = 0; H_E4_PT = 0; Aktstar = 0; SigAP_T = 0; E = 10/membrane; H = 10/membrane; fint = 0; pERK = 0; ERK_MEKstar = 0; pERK_MEKstar = 0; pERK_ERKpase = 0; ERKpase = 0; ERKstar_ERKpase = 35/membrane; // Compartment initializations: membrane = 1; // Variable initializations: ErbB1_Abund = 274; ErbB2_Abund = 158; ErbB3_Abund = 294; ErbB4_Abund = 399; Grb2_Abund = 82.4; Shc_Abund = 11.5; PI3K_Abund = 46.4; RasGAP_Abund = 93.6; SOS_Abund = 82.3; Gab1_Abund = 43.1; PIP2_Abund = 197; Akt_Abund = 444.2921; Ras_Abund = 95.7; Raf_Abund = 743; MEK_Abund = 772; ERK_Abund = 749.9716; VmaxPY = 223.8776; KmPY = 486.1398; kdeg = 0.0259; kf47 = 24.6048; Vmaxr47 = 590.5058; Kmf47 = 698.6022; Kmr47 = 483.8622; kf48 = 16.833; Kmf48 = 715.5688; Kmr48 = 324.9294; PTEN = 693.5786; kf49 = 44.3501; kr49 = 552.6746; Kmf49 = 343.2483; Kmr49 = 753.1667; Kmr49b = 381.2208; kr49b = 640.8212; kf51 = 3.6515; kr51 = 0; Vmaxr51 = 16.737; Kmf51 = 599.7076; Kmr51 = 346.4779; Kmrb51 = 988.4496; kf52 = 0.7745; Vmaxr52 = 199.2773; Kmf52 = 545.4408; Kmr52 = 675.2994; kf53 = 0.6094; Vmaxr53 = 59.2314; Kmf53 = 812.254; Kmr53 = 944.7692; kf54 = 0.0538; Vmaxr54 = 588.2671; Kmf54 = 457.9645; Kmr54 = 336.183; kf55 = 0.2256; Vmaxr55 = 646.9003; Kmf55 = 460.9446; Kmr55 = 643.9247; kf38 = 279.9929; kf39 = 385.7428; kf50 = 389.1061; a98 = 0.0849; b98 = 0.1833; koff46 = 0.5194; EGF_off = 0.0175; HRGoff_3 = 0.0009; HRGoff_4 = 0.0973; koff4 = 0.1717; koff5 = 4.3985; koff6 = 2.6619; koff7 = 8.0557; koff8 = 9.1034; koff9 = 5.5425; koff57 = 0.4526; koff16 = 0.5737; koff17 = 4.6874; koff18 = 2.2768; koff19 = 2.3361; koff20 = 0.6761; koff21 = 4.7291; koff22 = 3.6962; koff23 = 2.3619; koff24 = 4.4226; koff25 = 2.225; koff26 = 0.0103; koff27 = 1.8922; koff28 = 4.6432; koff29 = 2.0148; koff30 = 4.9936; koff31 = 1.2204; koff32 = 3.8752; koff33 = 1.2817; koff34 = 3.2036; koff35 = 1.8696; koff36 = 1.2567; koff37 = 0.4059; koff65 = 0.1185; koff66 = 2.2988; koff67 = 1.6142; koff40 = 3.1051; koff41 = 7.0487; koff42 = 3.5195; koff43 = 0.5441; koff44 = 0.4265; koff45 = 3.9967; koff58 = 6.3059; koff59 = 9.172; koff68 = 2.8871; PTP1B_Abund = 500; kPTP10 = 29.8531; kPTP11 = 78.204; kPTP12 = 11.4211; kPTP13 = 55.2104; kPTP14 = 57.7506; kPTP15 = 60.2628; kPTP63 = 7.4766; kPTP64 = 48.6335; koff73 = 3.0048; koff74 = 1.2496; koff75 = 1.4323; koff76 = 2.1542; koff77 = 1.2237; koff78 = 0.2007; koff79 = 1.1852; koff80 = 2.9373; kPTP38 = 83.4465; kPTP39 = 79.6132; koff88 = 3.9255; kPTP50 = 96.5716; kf81 = 1.361; Vmaxr81 = 242.6034; Kmf81 = 485.2626; Kmr81 = 323.4012; kf82 = 6.9987; Vmaxr82 = 398.1931; Kmf82 = 781.4374; Kmr82 = 595.8395; kf83 = 1.7628; Vmaxr83 = 534.0531; Kmf83 = 609.4766; Kmr83 = 653.5184; kf84 = 4.6894; Vmaxr84 = 634.1626; Kmf84 = 622.3847; Kmr84 = 258.4637; kf85 = 6.7591; Vmaxr85 = 369.2261; Kmf85 = 179.6486; Kmr85 = 290.7667; kcon49 = 9.9783; kon1 = 0.00010086; kon86 = 0.0038; kon2 = 0.0059; kon3 = 0.0334; kon87 = 0.0008; kon4 = 0.5005; kon5 = 2.5427; kon6 = 0.2283; kon7 = 1.0606; kon8 = 1.0259; kon9 = 2.2868; kon57 = 0.0039; kf10 = 0.6496; kf11 = 0.3721; kf12 = 1.8012; kf13 = 0.8875; kf14 = 6.1726; kf15 = 1.3565; kf63 = 0.9297; kf64 = 1.2083; kon16 = 0.0097; kon17 = 0.0049; kon18 = 0.0117; kon73 = 0.0116; kon19 = 0.0896; kon20 = 0.0478; kon21 = 0.0114; kon74 = 0.0133; kon22 = 0.0007; kon23 = 0.0138; kon24 = 0.005; kon25 = 0.0995; kon75 = 0.0137; kon26 = 0.0355; kon27 = 0.0201; kon28 = 0.0074; kon29 = 0.0346; kon76 = 0.0053; kon30 = 0.002; kon31 = 0.0032; kon32 = 0.0009; kon33 = 0.0335; kon77 = 0.0101; kon34 = 0.0001; kon35 = 0.0602; kon36 = 0.0043; kon37 = 0.0791; kon78 = 0.0076; kon79 = 0.0078; kon65 = 0.0123; kon66 = 0.00019264; kon67 = 6.6667e-005; kon80 = 0.0002; kon40 = 0.0191; kon41 = 0.0051; kon42 = 0.0023; kon43 = 0.0127; kon44 = 0.0122; kon45 = 0.0028; kon88 = 0.0108; kon46 = 0.0148; kon58 = 0.0215; kon59 = 0.0077; kon60 = 0.00011994; VeVc = 33.3; koff60 = 4.9981; koff61 = 5.229; kon61 = 0.8048; kon62 = 1.782; koff62 = 5.5142; kon68 = 0.0045; kon69 = 0.0084; koff69 = 3.97; kon70 = 0.0116; koff70 = 2.6069; kon71 = 0.0078; koff71 = 2.2988; kon72 = 0.0355; koff72 = 0.907; eps = 1e-016; kon89 = 0.1997; koff89 = 99.9637; kcat90 = 20.0037; kon91 = 0.1966; koff91 = 99.9983; kcat92 = 0.2004; kon93 = 0.2003; koff93 = 100.0037; kcat94 = 0.9966; kon95 = 0.1993; koff95 = 100.0023; kcat96 = 19.9851; ERKPpase_Abund = 35.005; // Other declarations: const membrane, ErbB1_Abund, ErbB2_Abund, ErbB3_Abund, ErbB4_Abund, Grb2_Abund; const Shc_Abund, PI3K_Abund, RasGAP_Abund, SOS_Abund, Gab1_Abund, PIP2_Abund; const Akt_Abund, Ras_Abund, Raf_Abund, MEK_Abund, ERK_Abund, VmaxPY, KmPY; const kdeg, kf47, Vmaxr47, Kmf47, Kmr47, kf48, Kmf48, Kmr48, PTEN, kf49; const kr49, Kmf49, Kmr49, Kmr49b, kr49b, kf51, kr51, Vmaxr51, Kmf51, Kmr51; const Kmrb51, kf52, Vmaxr52, Kmf52, Kmr52, kf53, Vmaxr53, Kmf53, Kmr53; const kf54, Vmaxr54, Kmf54, Kmr54, kf55, Vmaxr55, Kmf55, Kmr55, kf38, kf39; const kf50, a98, b98, koff46, EGF_off, HRGoff_3, HRGoff_4, koff4, koff5; const koff6, koff7, koff8, koff9, koff57, koff16, koff17, koff18, koff19; const koff20, koff21, koff22, koff23, koff24, koff25, koff26, koff27, koff28; const koff29, koff30, koff31, koff32, koff33, koff34, koff35, koff36, koff37; const koff65, koff66, koff67, koff40, koff41, koff42, koff43, koff44, koff45; const koff58, koff59, koff68, PTP1B_Abund, kPTP10, kPTP11, kPTP12, kPTP13; const kPTP14, kPTP15, kPTP63, kPTP64, koff73, koff74, koff75, koff76, koff77; const koff78, koff79, koff80, kPTP38, kPTP39, koff88, kPTP50, kf81, Vmaxr81; const Kmf81, Kmr81, kf82, Vmaxr82, Kmf82, Kmr82, kf83, Vmaxr83, Kmf83, Kmr83; const kf84, Vmaxr84, Kmf84, Kmr84, kf85, Vmaxr85, Kmf85, Kmr85, kcon49; const kon1, kon86, kon2, kon3, kon87, kon4, kon5, kon6, kon7, kon8, kon9; const kon57, kf10, kf11, kf12, kf13, kf14, kf15, kf63, kf64, kon16, kon17; const kon18, kon73, kon19, kon20, kon21, kon74, kon22, kon23, kon24, kon25; const kon75, kon26, kon27, kon28, kon29, kon76, kon30, kon31, kon32, kon33; const kon77, kon34, kon35, kon36, kon37, kon78, kon79, kon65, kon66, kon67; const kon80, kon40, kon41, kon42, kon43, kon44, kon45, kon88, kon46, kon58; const kon59, kon60, VeVc, koff60, koff61, kon61, kon62, koff62, kon68, kon69; const koff69, kon70, koff70, kon71, koff71, kon72, koff72, eps, kon89, koff89; const kcat90, kon91, koff91, kcat92, kon93, koff93, kcat94, kon95, koff95; const kcat96, ERKPpase_Abund; // Unit definitions: unit substance = 1e-9 mole; // Display Names: substance is "nanomole"; E1 is "ErbB1"; E2 is "ErbB2"; E3 is "ErbB3"; E4 is "ErbB4"; E_E1 is "EGF-ErbB1"; H_E3 is "HRG-ErbB3"; H_E4 is "HRG-ErbB4"; E11 is "(EGF-ErbB1)2"; E12 is "EGF-ErbB1-ErbB2"; E23 is "HRG-ErbB3-ErbB2"; E34 is "(HRG-ErbB3/4)2"; E24 is "HRG-Erb4-ErbB2"; E44 is "(HRG-Erb4)2"; E11P is "E11_p"; E12P is "E12_p"; E23P is "E23_p"; E34P is "E34_p"; E24P is "E24_p"; E44P is "E44_p"; G is "Grb2"; S is "Shc"; I is "PI-3K"; R is "RasGAP"; O is "SOS"; A is "Gab1"; E11G is "E11-Grb2"; E11S is "E11-Shc"; E11R is "E11-RasGAP"; E12G is "E12-Grb2"; E12S is "E12-Shc"; E12R is "E12-RasGAP"; E23G is "E23-Grb2"; E23S is "E23-Shc"; E23I is "E23-PI-3K"; E23R is "E23-RasGAP"; E34G is "E34-Grb2"; E34S is "E34-Shc"; E34I is "E34-PI-3K"; E34R is "E34-RasGAP"; E24G is "E24-Grb2"; E24S is "E24-Shc"; E24I is "E24-PI-3K"; E24R is "E24-RasGAP"; E44G is "E44-Grb2"; E44S is "E44-Shc"; E44I is "E44-PI-3K"; E44R is "E44-RasGAP"; SigG is "Sum Grb2"; SigS is "Sum Shc"; SigI is "Sum PI-3K"; SigR is "Sum RasGAP"; SigA is "Sum Gab1"; SigSP is "Sum Shc_p"; SigAP is "Sum Gab1_p"; SigG_O is "Sum Grb2-SOS"; SigG_A is "Sum Grb2-Gab1"; SigSP_G is "Sum Shc_p-Grb2"; SigAP_S is "Sum Gab1_p-Shc"; SigAP_I is "Sum Gab1_p-PI-3K"; SigAP_R is "Sum Gab1_p-RasGAP"; P3_A is "PIP3-Gab1"; P2 is "PIP2"; P3 is "PIP3"; RsD is "RasGDP"; RsT is "RasGTP"; SigRP is "Sum RasGAP_p"; Rafstar is "Raf*"; MEKstar is "MEK*"; ERKstar is "ERK*"; OP is "SOS_p"; AP is "Gab1_p"; A_SigG_O is "Gab1_SumGrb2-SOS"; SigA_G is "Sum PIP3-Gab1-Grb2"; SigA_G_O is "Sum PIP3-Gab1-Grb2_SOS"; SigO is "Sum SOS"; E13 is "ErbB1-ErbB3"; E14 is "ErbB1-ErbB4"; E13P is "ErbB1-ErbB3_p"; E14P is "ErbB1-ErbB3_p"; E13G is "E13-Grb2"; E13S is "E13-Shc"; E13I is "E13-PI-3K"; E13R is "E13-RasGAP"; E14G is "E14-Grb2"; E14S is "E14-Shc"; E14I is "E14-PI-3K"; E14R is "E14-RasGAP"; T is "PTP-1B"; E11T is "E11-PTP-1B"; E12T is "E12-PTP-1B"; E23T is "E23-PTP-1B"; E34T is "E34-PTP-1B"; E24T is "E24-PTP-1B"; E44T is "E44-PTP-1B"; E13T is "E13-PTP-1B"; E14T is "E14-PTP-1B"; SigT is "Sig-PTP-1B"; E1_PT is "E1_p-PTP-1B"; E2_PT is "E2_p-PTP-1B"; E4_PT is "E4_p-PTP-1B"; E_E1_PT is "E_E1_p-PTP-1B"; H_E4_PT is "H_E4_p-PTP-1B"; SigAP_T is "SumGab1_p-PTP-1B"; E is "EGF"; H is "HRG"; pERK is "p_ERK"; ERK_MEKstar is "ERK-MEK*"; pERK_MEKstar is "p_ERK-MEK*"; pERK_ERKpase is "p_ERK-ERKpase"; ERKstar_ERKpase is "ERK*-ERKpase"; norm_Akt_star is "normalized Akt*"; norm_Erk_star is "normalized Erk*"; EGF_Binding_to_ErbB1 is "EGF Binding to ErbB1"; HRG_Binding_to_ErbB3 is "HRG Binding to ErbB3"; HRG_Binding_to_ErbB4 is "HRG Binding to ErbB4"; ErbB1_Dimerization is "ErbB1 Dimerization"; ErbB1ErbB2_Heterodimerization is "ErbB1/ErbB2 Heterodimerization"; ErbB2ErbB3_Heterodimerization is "ErbB2/ErbB3 Heterodimerization"; ErbB3ErbB4_Heterodimerization is "ErbB3/ErbB4 Heterodimerization"; ErbB2ErbB4_Heterodimerization is "ErbB2/ErbB4 Heterodimerization"; ErbB4_Homodimerization is "ErbB4 Homodimerization"; Net_E11_Phosphorylation is "Net E11 Phosphorylation"; Net_E12_Phosphorylation is "Net E12 Phosphorylation"; Net_E23_Phosphorylation is "Net E23 Phosphorylation"; Net_E34_Phosphorylation is "Net E34 Phosphorylation"; Net_E24_Phosphorylation is "Net E24 Phosphorylation"; Net_E44_Phosphorylation is "Net E44 Phosphorylation"; Net_E11PGrb2_binding is "Net E11P/Grb2 binding"; Net_E11PShc_binding is "Net E11P/Shc binding"; Net_E11PRasGAP_binding is "Net E11P/RasGAP binding"; Net_E12PGrb2_binding is "Net E12P/Grb2 binding"; Net_E12PShc_binding is "Net E12P/Shc binding"; Net_E12PRasGAP_binding is "Net E12P/RasGAP binding"; Net_E23PGrb2_binding is "Net E23P/Grb2 binding"; Net_E23PShc_binding is "Net E23P/Shc binding"; Net_E23PPI3K_binding is "Net E23P/PI3K binding"; Net_E23PRasGAP_binding is "Net E23P/RasGAP binding"; Net_E34PGrb2_binding is "Net E34P/Grb2 binding"; Net_E34PShc_binding is "Net E34P/Shc binding"; Net_E34PPI3K_binding is "Net E34P/PI3K binding"; Net_E34PRasGAP_binding is "Net E34P/RasGAP binding"; Net_E24PGrb2_binding is "Net E24P/Grb2 binding"; Net_E24PShc_binding is "Net E24P/Shc binding"; Net_E24PPI3K_binding is "Net E24P/PI3K binding"; Net_E24PRasGAP_binding is "Net E24P/RasGAP binding"; Net_E44PRasGAP_binding_1 is "Net E44P/RasGAP binding"; Net_E44PShc_binding is "Net E44P/Shc binding"; Net_E44PPI3K_binding is "Net E44P/PI3K binding"; Net_E44PRasGAP_binding_2 is "Net E44P/RasGAP binding"; Net_Shc_Phosphorylation is "Net Shc Phosphorylation"; Net_Gab1_Phosphorylation is "Net Gab1 Phosphorylation"; Net_Grb2SOS_binding is "Net Grb2/SOS binding"; Net_Grb2Gab1_binding is "Net Grb2/Gab1 binding"; Net_ShcGrb2_binding is "Net Shc/Grb2 binding"; Net_Gab1Shc_binding is "Net Gab1/Shc binding"; Net_Gab1PI3K_binding is "Net Gab1/PI3K binding"; Net_Gab1RasGAP_binding is "Net Gab1/RasGAP binding"; Net_Gab1PIP3_binding is "Net Gab1/PIP3 binding"; Net_Akt_Activation is "Net Akt Activation"; Net_PIP3_Production is "Net PIP3 Production"; Net_RasGTP_Production is "Net RasGTP Production"; Net_RasGAP_Phosphorylation is "Net RasGAP Phosphorylation"; Net_Raf_Activation is "Net Raf Activation"; Net_MEK_Activation is "Net MEK Activation"; Net_SOS_ST_Phosphorylation is "Net SOS S/T Phosphorylation"; Net_Gab1_ST_Phosphorylation is "Net Gab1 S/T Phosphorylation"; Grb2_binding_to_P3_A is "Grb2 binding to P3_A"; SOS_binding_to_SigAG is "SOS binding to SigA-G"; Gab1_binding_to_SigGO is "Gab1 binding to SigG-O"; SOS_binding_to_SigGA is "SOS binding to SigG-A"; ErbB1ErbB3_Heterodimerization is "ErbB1/ErbB3 Heterodimerization"; ErbB1ErbB4_Heterodimerization is "ErbB1/ErbB4 Heterodimerization"; Net_E13_Phosphorylation is "Net E13 Phosphorylation"; Net_E14_Phosphorylation is "Net E14 Phosphorylation"; Net_E13Grb2_Binding is "Net E13/Grb2 Binding"; Net_E13Shc_Binding is "Net E13/Shc Binding"; Net_E13PI3K_Binding is "Net E13/PI3K Binding"; Net_E13RasGAP_Binding is "Net E13/RasGAP Binding"; Net_E14Grb2_Binding is "Net E14/Grb2 Binding"; Net_E14Shc_Binding is "Net E14/Shc Binding"; Net_E14PI3K_Binding is "Net E14/PI3K Binding"; Net_E14RasGAP_Binding is "Net E14/RasGAP Binding"; Net_E11PTP1B_Binding is "Net E11/PTP1B Binding"; Net_E12PTP1B_Binding is "Net E12/PTP1B Binding"; Net_E23PTP1B_Binding is "Net E23/PTP1B Binding"; Net_E34PTP1B_Binding is "Net E34/PTP1B Binding"; Net_E24PTP1B_Binding is "Net E24/PTP1B Binding"; Net_E44PTP1B_Binding is "Net E44/PTP1B Binding"; Net_E13PTP1B_Binding is "Net E13/PTP1B Binding"; Net_E14PTP1B_Binding is "Net E14/PTP1B Binding"; Net_E1_ST_Phosphorylation is "Net E1 S/T Phosphorylation"; Net_E2_ST_Phosphorylation is "Net E2 S/T Phosphorylation"; Net_E4_ST_Phosphorylation is "Net E4 S/T Phosphorylation"; Net_E_E1_ST_Phosphorylation is "Net E_E1 S/T Phosphorylation"; Net_H_E4_ST_Phosphorylation is "Net H_E4 S/T Phosphorylation"; EGF_binding_to_E1PT is "EGF binding to E1-PT"; HRG_binding_to_E4PT is "HRG binding to E4-PT"; PTP1B_binding_to_SigAP is "PTP1B binding to SigAP"; E11P_Degradation is "E11P Degradation"; E11G_Degradation is "E11G Degradation"; E11S_Degradation is "E11S Degradation"; E11R_Degradation is "E11R Degradation"; E11T_Degradation is "E11T Degradation"; mwbbde76d1_155c_4264_8447_4457527547cb is "1-1 Dimer Internalization Fraction"; EGF_in_EC_compartment is "EGF in EC compartment"; HRG_in_EC_compartment is "HRG in EC compartment"; ERK_binding_to_MEKstar_1 is "ERK binding to MEKstar"; pERK_production is "pERK production"; ERK_binding_to_MEKstar_2 is "ERK binding to MEKstar"; ERKstar_production is "ERKstar production"; ERKstar_binding_to_Phosphatase is "ERKstar binding to Phosphatase"; ERKstar_dephosphorylation is "ERKstar dephosphorylation"; pERK_binding_to_Phosphatase is "pERK binding to Phosphatase"; pERK_dephosphorylation is "pERK dephosphorylation"; end