#faratian1



#reactions
R1:
 {1.0}E3 + {1.0}HRG = {1.0}E3H
  k1 * (E3 * HRG - Kd_1 * E3H)
R10:
 {1.0}ShcP = {1.0}Shc
  V10 * ShcP / (K10 + ShcP)
R11:
 {1.0}RasGDP = {1.0}RasGTP
  k11 * RasGDP * ShGS / (K11 + RasGDP)
R12:
 {1.0}RasGTP = {1.0}RasGDP
  V12 * RasGTP / (K12 + RasGTP)
R13:
 {1.0}Raf = {1.0}Rafa
  k13 * Raf * RasGTP / (K13 + Raf)
R14:
 {1.0}Rafa = {1.0}Raf
  k14 * Rafa * (Akt_PI_PP + E_raf) / (Rafa + K14)
R15:
 {1.0}MEK = {1.0}MEKP
  k15 * MEK * Rafa / (K15 + MEK)
R16_1:
 {1.0}MEKP + {1.0}PP2A = {1.0}MEKP_PP2A
  k16 * MEKP * PP2A
R16_2:
 {1.0}MEKP_PP2A = {1.0}MEK_PP2A
  k16_kat * MEKP_PP2A
R16_3:
 {1.0}MEK_PP2A = {1.0}MEK + {1.0}PP2A
  k18 * MEK_PP2A
R17_1:
 {1.0}MEKP = {1.0}MEKPP
  k15 * MEKP * Rafa / (K15 + MEKP)
R18_1:
 {1.0}MEKPP + {1.0}PP2A = {1.0}MEKPP_PP2A
  k16 * (PP2A * MEKPP - Kd_16 * MEKPP_PP2A)
R18_2:
 {1.0}MEKPP_PP2A = {1.0}MEKP_PP2A
  k16_kat * MEKPP_PP2A
R18_3:
 {1.0}MEKP_PP2A = {1.0}MEKP + {1.0}PP2A
  k22 * MEKP_PP2A
R19:
 {1.0}ERK = {1.0}ERKP
  k23 * ERK * MEKPP / (K23 + ERK)
R2:
 {1.0}E2 + {1.0}E3H = {1.0}E23H
  k2 * (E3H * E2 - Kd_2 * E23H)
R20:
 {1.0}ERKP = {1.0}ERK
  V24 * ERKP / (K24 + ERKP)
R21:
 {1.0}ERKP = {1.0}ERKPP
  k23 * ERKP * MEKPP / (K23 + ERKP)
R22:
 {1.0}ERKPP = {1.0}ERKP
  V24 * ERKPP / (K24 + ERKPP)
R23:
 {1.0}E23HP + {1.0}PI3K = {1.0}E23HP_PI3K
  k27 * (E23HP * PI3K - Kd_27 * E23HP_PI3K)
R24:
 {1.0}E23HP_PI3K = {1.0}E23HP_PI3Ka
  k28 * (E23HP_PI3K - k_28 * E23HP_PI3Ka)
R25:
 {1.0}E23HP_PI3Ka = {1.0}E23HP + {1.0}PI3Ka
  k29 * E23HP_PI3Ka - k_29 * E23HP * PI3Ka
R26:
 {1.0}PI3Ka = {1.0}PI3K
  V30 * PI3Ka
R27_1:
 {1.0}PI2 + {1.0}PI3Ka = {1.0}PI3Ka_PI
  k31 * (PI2 * PI3Ka - K_d31 * PI3Ka_PI)
R28_1:
 {1.0}PIP3 + {1.0}PTEN = {1.0}PTEN_PIP3
  k32 * (PIP3 * PTEN - Kd_32 * PTEN_PIP3)
R28_2:
 {1.0}PTEN_PIP3 = {1.0}PTEN_PI
  k33 * PTEN_PIP3
R28_3:
 {1.0}PTEN_PI = {1.0}PI2 + {1.0}PTEN
  k34 * PTEN_PI
R28_4:
 {1.0}PTEN = {1.0}PTENP
  V35 * PTEN / (K35 + PTEN)
R28_5:
 {1.0}PTEN + {1.0}PTENP = {1.0}PTENP_PTEN
  k36 * (PTEN * PTENP - Kd_36 * PTENP_PTEN)
R28_6:
 {1.0}PTENP_PTEN = {1.0}PTEN_PTEN
  k37 * PTENP_PTEN
R28_7:
 {1.0}PTEN_PTEN = {2.0}PTEN
  k38 * PTEN_PTEN
R29:
 {1.0}PIP3 + {1.0}Akt = {1.0}Akt_PIP3
  k39 * (PIP3 * Akt - Kd_39 * Akt_PIP3)
R3:
 {1.0}E23H = {1.0}E23HP
  k3 * (E23H - Kd_3 * E23HP)
R30:
 {1.0}Akt_PIP3 = {1.0}Akt_PI_P
  V40 * Akt_PIP3 / (K40 + Akt_PIP3)
R31_1:
 {1.0}Akt_PI_P + {1.0}PP2A = {1.0}Akt_PI_P_PP2A
  k41 * Akt_PI_P * PP2A
R31_2:
 {1.0}Akt_PI_P_PP2A = {1.0}Akt_PIP3_PP2A
  k42 * Akt_PI_P_PP2A
R31_3:
 {1.0}Akt_PIP3_PP2A = {1.0}Akt_PIP3 + {1.0}PP2A
  k43 * Akt_PIP3_PP2A
R32:
 {1.0}Akt_PI_P = {1.0}Akt_PI_PP
  V40 * Akt_PI_P / (K40 + Akt_PI_P)
R33_1:
 {1.0}Akt_PI_PP + {1.0}PP2A = {1.0}Akt_PI_PP_PP2A
  k41 * (Akt_PI_PP * PP2A - Kd_41 * Akt_PI_PP_PP2A)
R33_2:
 {1.0}Akt_PI_PP_PP2A = {1.0}Akt_PI_P_PP2A
  k42 * Akt_PI_PP_PP2A
R33_3:
 {1.0}Akt_PI_P_PP2A = {1.0}Akt_PI_P + {1.0}PP2A
  k47 * Akt_PI_P_PP2A
R34:
 {1.0}E23HP = $pool
  k48 * E23HP
R35:
 {1.0}E2 + {1.0}Per = {1.0}E2_Per
  k49 * (Per * E2 - Kd_49 * E2_Per)
R36:
 {1.0}E2_Per = {1.0}E2Per
  k50 * E2_Per - k_50 * E2Per
R37:
 {1.0}E3H = {1.0}E3H_C
  k51 * E3H
R38:
 {1.0}E2 + {1.0}E3H_C = {1.0}E23H
  k2 * (E3H_C * E2 - Kd_2 * E23H)
R39:
 {1.0}E23H = {1.0}E23H_C
  k53 * E23H
R4:
 {1.0}E23HP = {1.0}E23H
  V4 * E23HP / (K4 + E23HP)
R40:
 {1.0}E23H_C = {1.0}E23HP
  k3 * (E23H_C - Kd_3 * E23HP)
R41:
 {1.0}PI3Ka_PI = {1.0}PI3Ka_PIP3
  k55 * PI3Ka_PI
R42:
 {1.0}PI3Ka_PIP3 = {1.0}PI3Ka + {1.0}PIP3
  k56 * PI3Ka_PIP3
R43:
 {1.0}PTEN = {1.0}PTEN_bpV
  k57 * (PTEN * bpV - Kd_57 * PTEN_bpV)
R44:
 {1.0}PI3K = {1.0}PI3K_LY
  k58 * (PI3K * LY - Kd_58 * PI3K_LY)
R5:
 {1.0}E23HP + {1.0}Shc = {1.0}E23HP_Shc
  k5 * (E23HP * Shc - Kd_5 * E23HP_Shc)
R6:
 {1.0}E23HP_Shc = {1.0}E23HP_ShcP
  k6 * E23HP_Shc - k_6 * E23HP_ShcP
R7:
 {1.0}E23HP_ShcP + {1.0}GS = {1.0}E23HP_ShGS
  k7 * (E23HP_ShcP * GS - Kd_7 * E23HP_ShGS)
R8:
 {1.0}E23HP_ShGS = {1.0}E23HP + {1.0}ShGS
  k8 * (E23HP_ShGS - Kd_8 * E23HP * ShGS)
R9:
 {1.0}ShGS = {1.0}GS + {1.0}ShcP
  k9 * (ShGS - k_9 * ShcP * GS)


#parameters
Akt0 = 10.0
E3_0 = 0.0
E_raf = 7.0
K10 = 340.0
K11 = 0.18
K12 = 0.1
K13 = 11.7
K14 = 50.0
K15 = 1.0
K23 = 10.0
K24 = 10.0
K35 = 2.0
K4 = 50.0
K40 = 0.1
K_d31 = 100.0
Kd_1 = 600.0
Kd_16 = 1.0
Kd_2 = 10.0
Kd_27 = 1.0
Kd_3 = 0.1
Kd_32 = 0.01
Kd_36 = 2.2
Kd_39 = 20.0
Kd_41 = 0.1
Kd_49 = 20000.0
Kd_5 = 1.0
Kd_57 = 10.0
Kd_58 = 80.0
Kd_7 = 9.0
Kd_8 = 0.1
LY = 0.0
PI0 = 70.0
PI3K_CY = 0.0
Pool_10_ = 10.0
Pool_11_ = 100.0
Pool_12_ = 120.0
Pool_13_ = 100.0
Pool_14_ = 100.0
Pool_1_ = 2900.0
Pool_2_ = -2920.0
Pool_3_ = 200.0
Pool_4_ = 50.0
Pool_5_ = 300.0
Pool_6_ = 0.0
Pool_7_ = 10.0
Pool_8_ = 100.0
Pool_9_ = 10.0
V10 = 0.0154
V12 = 3.0
V24 = 1.8
V30 = 900.0
V35 = 150.0
V4 = 10.0
V40 = 15000.0
bpV = 0.0
k1 = 0.005
k11 = 6.0
k13 = 1.0
k14 = 0.6
k15 = 2.1
k16 = 0.06
k16_kat = 0.6
k18 = 0.6
k2 = 10.0
k22 = 0.06
k23 = 1.2
k27 = 3.0
k28 = 300.0
k29 = 13520.0
k3 = 1.0
k31 = 0.03
k32 = 8000.0
k33 = 15.0
k34 = 3.6
k36 = 1.0
k37 = 150.0
k38 = 150.0
k39 = 15000.0
k41 = 3.0
k42 = 45.0
k43 = 30.0
k47 = 0.3
k48 = 0.001
k49 = 0.003
k5 = 0.06
k50 = 0.6
k51 = 0.01
k53 = 0.01
k55 = 30.0
k56 = 30.0
k57 = 100.0
k58 = 100.0
k6 = 12.0
k7 = 36.0
k8 = 12.0
k9 = 35.0
k_28 = 0.0
k_29 = 0.0
k_50 = 0.012
k_6 = 3.0
k_9 = 0.0
mu = 0.0
pAkt_max = 91.0
scal = 1.0
scall = 0.6
scalll = 30.0
sens = 0.0
tE3P_max = 65.0
tERKP_max = 10.0
Default = 1.0


#initial values
Akt = 100.0
Akt_PIP3 = 0.0
Akt_PIP3_PP2A = 0.0
Akt_PI_P = 0.0
Akt_PI_PP = 0.0
Akt_PI_PP_PP2A = 0.0
Akt_PI_P_PP2A = 0.0
E2 = 100.0
E23H = 0.0
E23HP = 0.0
E23HP_PI3K = 0.0
E23HP_PI3Ka = 0.0
E23HP_ShGS = 0.0
E23HP_Shc = 0.0
E23HP_ShcP = 0.0
E23H_C = 0.0
E2Per = 0.0
E2_Per = 0.0
E3 = 80.0
E3H = 0.0
E3H_C = 0.0
ERK = 10.0
ERKP = 0.0
ERKPP = 0.0
GS = 100.0
HRG = 3000.0
MEK = 10.0
MEKP = 0.0
MEKPP = 0.0
MEKPP_PP2A = 0.0
MEKP_PP2A = 0.0
MEK_PP2A = 0.0
PI2 = 300.0
PI3K = 200.0
PI3K_LY = 0.0
PI3Ka = 0.0
PI3Ka_PI = 0.0
PI3Ka_PIP3 = 0.0
PIP3 = 8.05772e-12
PP2A = 10.0
PTEN = 42.7798
PTENP = 3.39885
PTENP_PTEN = 0.955337
PTEN_PI = 5.02914e-08
PTEN_PIP3 = 3.14554e-08
PTEN_PTEN = 0.955337
PTEN_bpV = 0.0
Per = 0.0
Raf = 100.0
Rafa = 0.0
RasGDP = 120.0
RasGTP = 0.0
ShGS = 0.0
Shc = 100.0
ShcP = 0.0


#assignment rules
!F tERKP = (ERKP + ERKPP) / tERKP_max
!F pAkt = (Akt_PI_PP + Akt_PI_P + Akt_PI_PP_PP2A + Akt_PI_P_PP2A) / pAkt_max
!F tPTENP = PTENP / 7.6
!F tPTEN = PTENP + PTEN + PTENP_PTEN + PTEN_PTEN + PTEN_PIP3 + PTEN_PI
!F tE3P = (E23HP + E23HP_PI3K + E23HP_PI3Ka + E23HP_Shc + E23HP_ShcP + E23HP_ShGS) / tE3P_max