#neves1



#reactions
A1:
 {1.0}c2_R2C2_cyto + {1.0}cAMP_cyto = {1.0}c3_R2C2_cyto
  (Kf * 0.00166112956810631 * c2_R2C2_cyto * 0.00166112956810631 * cAMP_cyto + -(Kr * 0.00166112956810631 * c3_R2C2_cyto)) * cyto * 1 * (1 / KMOLE)
A2:
 {1.0}c3_R2C2_cyto + {1.0}cAMP_cyto = {1.0}PKA_cyto
  (Kf * 0.00166112956810631 * c3_R2C2_cyto * 0.00166112956810631 * cAMP_cyto + -(Kr * 0.00166112956810631 * PKA_cyto)) * cyto * 1 * (1 / KMOLE)
AC_activation:
 {1.0}G_a_s_cyto + {1.0}AC_cyto_mem = {1.0}AC_active_cyto_mem
  (Kf_AC_activation * 0.00166112956810631 * G_a_s_cyto * AC_cyto_mem + -(Kr_AC_activation * AC_active_cyto_mem)) * cyto_mem
AC_active:
 {1.0}ATP_cyto = {1.0}cAMP_cyto
  Vmax_AC_active_AC_active * 0.00166112956810631 * ATP_cyto * (1 / (Km_AC_active + 0.00166112956810631 * ATP_cyto)) * cyto_mem
AC_basal:
 {1.0}ATP_cyto = {1.0}cAMP_cyto
  Vmax_AC_basal_AC_basal * 0.00166112956810631 * ATP_cyto * (1 / (Km_AC_basal + 0.00166112956810631 * ATP_cyto)) * cyto_mem
B1:
 {1.0}R2C2_cyto + {1.0}cAMP_cyto = {1.0}c_R2C2_cyto
  (Kf * 0.00166112956810631 * R2C2_cyto * 0.00166112956810631 * cAMP_cyto + -(Kr * 0.00166112956810631 * c_R2C2_cyto)) * cyto * 1 * (1 / KMOLE)
B2:
 {1.0}c_R2C2_cyto + {1.0}cAMP_cyto = {1.0}c2_R2C2_cyto
  (Kf * 0.00166112956810631 * c_R2C2_cyto * 0.00166112956810631 * cAMP_cyto + -(Kr * 0.00166112956810631 * c2_R2C2_cyto)) * cyto * 1 * (1 / KMOLE)
GRK:
 {1.0}iso_BAR_cyto_mem = {1.0}iso_BAR_p_cyto_mem
  Vmax_grk_GRK * iso_BAR_cyto_mem * (1 / (Km_grk + iso_BAR_cyto_mem)) * cyto_mem
GRK_bg:
 {1.0}iso_BAR_cyto_mem = {1.0}iso_BAR_p_cyto_mem
  Vmax_GRK_bg_GRK_bg * iso_BAR_cyto_mem * (1 / (Km_GRK_bg + iso_BAR_cyto_mem)) * cyto_mem
GTPase:
 {1.0}G_a_s_cyto = {1.0}G_GDP_cyto
  (Kf_GTPase * 0.00166112956810631 * G_a_s_cyto + -(Kr_GTPase * 0.00166112956810631 * G_GDP_cyto)) * cyto * 1 * (1 / KMOLE)
G_binds_BAR:
 {1.0}BAR_cyto_mem + {1.0}G_protein_cyto = {1.0}BAR_G_cyto_mem
  (Kf_G_binds_BAR * BAR_cyto_mem * 0.00166112956810631 * G_protein_cyto + -(Kr_G_binds_BAR * BAR_G_cyto_mem)) * cyto_mem
G_binds_iso_BAR:
 {1.0}iso_BAR_cyto_mem + {1.0}G_protein_cyto = {1.0}iso_BAR_G_cyto_mem
  (Kf_G_binds_iso_BAR * iso_BAR_cyto_mem * 0.00166112956810631 * G_protein_cyto + -(Kr_G_binds_iso_BAR * iso_BAR_G_cyto_mem)) * cyto_mem
MEK_activates_MAPK:
 {1.0}MAPK_cyto = {1.0}MAPK_active_cyto
  Vmax_MEK_activates_MAPK * 0.00166112956810631 * MAPK_cyto * (1 / (Km + 0.00166112956810631 * MAPK_cyto)) * cyto * 1 * (1 / KMOLE)
PDE4:
 {1.0}cAMP_cyto = {1.0}AMP_cyto
  Vmax_PDE4_PDE4 * 0.00166112956810631 * cAMP_cyto * (1 / (Km_PDE4 + 0.00166112956810631 * cAMP_cyto)) * cyto * 1 * (1 / KMOLE)
PKA_P_PDE:
 {1.0}PDE4_cyto = {1.0}PDE4_P_cyto
  Vmax_PKA_P_PDE * 0.00166112956810631 * PDE4_cyto * (1 / (Km + 0.00166112956810631 * PDE4_cyto)) * cyto * 1 * (1 / KMOLE)
PKA_P_PTP:
 {1.0}PTP_cyto = {1.0}PTP_PKA_cyto
  Vmax_PKA_P_PTP * 0.00166112956810631 * PTP_cyto * (1 / (Km + 0.00166112956810631 * PTP_cyto)) * cyto * 1 * (1 / KMOLE)
PKA_activates_Raf:
 {1.0}B_Raf_cyto = {1.0}B_Raf_active_cyto
  Vmax_PKA_activates_Raf * 0.00166112956810631 * B_Raf_cyto * (1 / (Km + 0.00166112956810631 * B_Raf_cyto)) * cyto * 1 * (1 / KMOLE)
PPase_MAPK:
 {1.0}MAPK_active_cyto = {1.0}MAPK_cyto
  Vmax_PPase_MAPK * 0.00166112956810631 * MAPK_active_cyto * (1 / (Km + 0.00166112956810631 * MAPK_active_cyto)) * cyto * 1 * (1 / KMOLE)
PPase_Raf:
 {1.0}B_Raf_active_cyto = {1.0}B_Raf_cyto
  Vmax_PPase_Raf * 0.00166112956810631 * B_Raf_active_cyto * (1 / (Km + 0.00166112956810631 * B_Raf_active_cyto)) * cyto * 1 * (1 / KMOLE)
PPase_mek:
 {1.0}MEK_active_cyto = {1.0}MEK_cyto
  Vmax_PPase_mek * 0.00166112956810631 * MEK_active_cyto * (1 / (Km + 0.00166112956810631 * MEK_active_cyto)) * cyto * 1 * (1 / KMOLE)
PTP:
 {1.0}MAPK_active_cyto = {1.0}MAPK_cyto
  Vmax_PTP * 0.00166112956810631 * MAPK_active_cyto * (1 / (Km + 0.00166112956810631 * MAPK_active_cyto)) * cyto * 1 * (1 / KMOLE)
PTP_PKA:
 {1.0}MAPK_active_cyto = {1.0}MAPK_cyto
  Vmax_PTP_PKA * 0.00166112956810631 * MAPK_active_cyto * (1 / (Km + 0.00166112956810631 * MAPK_active_cyto)) * cyto * 1 * (1 / KMOLE)
Raf_activates_MEK:
 {1.0}MEK_cyto = {1.0}MEK_active_cyto
  Vmax_Raf_activates_MEK * 0.00166112956810631 * MEK_cyto * (1 / (Km + 0.00166112956810631 * MEK_cyto)) * cyto * 1 * (1 / KMOLE)
activate_Gs:
 {1.0}iso_BAR_G_cyto_mem = {1.0}iso_BAR_cyto_mem + {1.0}bg_cyto + {1.0}G_a_s_cyto
  (Kf_activate_Gs * iso_BAR_G_cyto_mem - Kr_activate_Gs * iso_BAR_cyto_mem * 0.00166112956810631 * bg_cyto * 0.00166112956810631 * G_a_s_cyto) * cyto_mem
bg_binds_GRK:
 {1.0}GRK_cyto + {1.0}bg_cyto = {1.0}GRK_bg_cyto
  (Kf_bg_binds_GRK * 0.00166112956810631 * GRK_cyto * 0.00166112956810631 * bg_cyto + -(Kr_bg_binds_GRK * 0.00166112956810631 * GRK_bg_cyto)) * cyto * 1 * (1 / KMOLE)
highKM_PDE:
 {1.0}cAMP_cyto = {1.0}AMP_cyto
  Vmax_highKM_PDE * 0.00166112956810631 * cAMP_cyto * (1 / (Km + 0.00166112956810631 * cAMP_cyto)) * cyto * 1 * (1 / KMOLE)
iso_binds_BAR:
 {1.0}BAR_cyto_mem + {1.0}iso_extra = {1.0}iso_BAR_cyto_mem
  (Kf * BAR_cyto_mem * 0.00166112956810631 * iso_extra + -(Kr * iso_BAR_cyto_mem)) * cyto_mem
iso_binds_BAR_g:
 {1.0}iso_extra + {1.0}BAR_G_cyto_mem = {1.0}iso_BAR_G_cyto_mem
  (Kf * 0.00166112956810631 * iso_extra * BAR_G_cyto_mem + -(Kr * iso_BAR_G_cyto_mem)) * cyto_mem
pde4_p:
 {1.0}cAMP_cyto = {1.0}AMP_cyto
  Vmax_pde4_p_pde4_p * 0.00166112956810631 * cAMP_cyto * (1 / (Km_pde4_p + 0.00166112956810631 * cAMP_cyto)) * cyto * 1 * (1 / KMOLE)
pp2a_4:
 {1.0}PDE4_P_cyto = {1.0}PDE4_cyto
  Vmax_pp2a_4_pp2a_4 * 0.00166112956810631 * PDE4_P_cyto * (1 / (Km_pp2a_4 + 0.00166112956810631 * PDE4_P_cyto)) * cyto * 1 * (1 / KMOLE)
pp_ptp:
 {1.0}PTP_PKA_cyto = {1.0}PTP_cyto
  Vmax_pp_ptp * 0.00166112956810631 * PTP_PKA_cyto * (1 / (Km + 0.00166112956810631 * PTP_PKA_cyto)) * cyto * 1 * (1 / KMOLE)
trimer:
 {1.0}bg_cyto + {1.0}G_GDP_cyto = {1.0}G_protein_cyto
  (Kf_trimer * 0.00166112956810631 * bg_cyto * 0.00166112956810631 * G_GDP_cyto + -(Kr_trimer * 0.00166112956810631 * G_protein_cyto)) * cyto * 1 * (1 / KMOLE)


#parameters
KMOLE = 0.00166112956810631
kcat_PKA_P_PTP = 0.2
kcat_PKA_activates_Raf = 10.0
kcat_PPase_MAPK = 0.636
kcat_PPase_Raf = 5.0
kcat_PPase_mek = 5.0
kcat_PTP = 1.06
kcat_PTP_PKA = 0.1
kcat_pp_ptp_pp_ptp = 5.0
activate_Gs_I = 0.0
activate_Gs_Kf_activate_Gs = 0.025
activate_Gs_Kr_activate_Gs = 0.0
pde4_p_Km_pde4_p = 1.3
PPase_Raf_Km = 15.7
iso_binds_BAR_I = 0.0
iso_binds_BAR_Kf = 1.0
iso_binds_BAR_Kr = 0.2
PDE4_Km_PDE4 = 1.3
bg_binds_GRK_Kf_bg_binds_GRK = 1.0
bg_binds_GRK_Kr_bg_binds_GRK = 0.25
MEK_activates_MAPK_Km = 0.046296
PKA_activates_Raf_Km = 0.5
AC_active_I = 0.0
AC_active_Km_AC_active = 32.0
GTPase_Kf_GTPase = 0.06667
GTPase_Kr_GTPase = 0.0
trimer_Kf_trimer = 6.0
trimer_Kr_trimer = 0.0
G_binds_iso_BAR_I = 0.0
G_binds_iso_BAR_Kf_G_binds_iso_BAR = 10.0
G_binds_iso_BAR_Kr_G_binds_iso_BAR = 0.1
A2_Kf = 8.35
A2_Kr = 0.0167
highKM_PDE_Km = 15.0
PKA_P_PTP_Km = 0.1
AC_activation_I = 0.0
AC_activation_Kf_AC_activation = 500.0
AC_activation_Kr_AC_activation = 1.0
AC_basal_I = 0.0
AC_basal_Km_AC_basal = 1030.0
B1_Kf = 0.0059
B1_Kr = 0.00028
GRK_I = 0.0
GRK_Km_grk = 15.0
PKA_P_PDE_Km = 0.5
Raf_activates_MEK_Km = 0.15909
PTP_PKA_Km = 9.0
B2_Kf = 0.0059
B2_Kr = 0.00028
PTP_Km = 0.46
iso_binds_BAR_g_I = 0.0
iso_binds_BAR_g_Kf = 1.0
iso_binds_BAR_g_Kr = 0.062
PPase_MAPK_Km = 0.77
pp2a_4_Km_pp2a_4 = 8.0
pp_ptp_Km = 6.0
GRK_bg_I = 0.0
GRK_bg_Km_GRK_bg = 4.0
G_binds_BAR_I = 0.0
G_binds_BAR_Kf_G_binds_BAR = 0.3
G_binds_BAR_Kr_G_binds_BAR = 0.1
PPase_mek_Km = 15.7
A1_Kf = 8.35
A1_Kr = 0.0167
cyto = 1.0
cyto_mem = 0.2
extra = 0.111111111111111


#initial values
AC_PKA_cyto_mem = 0.0
AC_active_cyto_mem = 0.0
AC_cyto_mem = 300.0
AMP_cyto = 3010000.0
ATP_cyto = 3010000.0
BAR_G_cyto_mem = 0.0
BAR_cyto_mem = 94.0
B_Raf_active_cyto = 0.0
B_Raf_cyto = 120.4
GRK_bg_cyto = 0.0
GRK_cyto = 0.602
G_GDP_cyto = 0.0
G_a_s_cyto = 0.0
G_protein_cyto = 2167.2
MAPK_active_cyto = 0.0
MAPK_cyto = 216.72
MEK_active_cyto = 0.0
MEK_cyto = 108.36
PDE4_P_cyto = 0.0
PDE4_cyto = 240.8
PDE_high_km_cyto = 301.0
PKA_cyto = 0.0
PP2A_cyto = 60.2
PP_PDE_cyto = 120.4
PTP_PKA_cyto = 0.0
PTP_PP_cyto = 60.2
PTP_cyto = 120.4
R2C2_cyto = 120.4
bg_cyto = 0.0
c2_R2C2_cyto = 0.0
c3_R2C2_cyto = 0.0
cAMP_cyto = 0.0
c_R2C2_cyto = 0.0
iso_BAR_G_cyto_mem = 0.0
iso_BAR_cyto_mem = 0.0
iso_BAR_p_cyto_mem = 0.0
iso_extra = 6020.0


#assignment rules
!F Vmax_pde4_p_pde4_p = 20.0 * 0.00166112956810631 * PDE4_P_cyto
!F Vmax_PPase_mek = kcat_PPase_mek * 0.00166112956810631 * PP2A_cyto
!F Vmax_GRK_bg_GRK_bg = 1.34 * 0.00166112956810631 * GRK_bg_cyto
!F Vmax_pp_ptp = kcat_pp_ptp_pp_ptp * 0.00166112956810631 * PTP_PP_cyto
!F Vmax_pp2a_4_pp2a_4 = 5.0 * 0.00166112956810631 * PP_PDE_cyto
!F Vmax_PPase_MAPK = kcat_PPase_MAPK * 0.00166112956810631 * PP2A_cyto
!F Vmax_PTP = kcat_PTP * 0.00166112956810631 * PTP_cyto
!F Vmax_PTP_PKA = kcat_PTP_PKA * 0.00166112956810631 * PTP_PKA_cyto
!F Vmax_Raf_activates_MEK = 0.105 * 0.00166112956810631 * B_Raf_active_cyto
!F Vmax_PKA_P_PDE = 10.0 * 0.00166112956810631 * PKA_cyto
!F Vmax_grk_GRK = 0.104 * 0.00166112956810631 * GRK_cyto
!F Vmax_AC_basal_AC_basal = 0.2 * AC_cyto_mem
!F Vmax_PKA_P_PTP = kcat_PKA_P_PTP * 0.00166112956810631 * PKA_cyto
!F Vmax_highKM_PDE = 8.0 * 0.00166112956810631 * PDE_high_km_cyto
!F Vmax_AC_active_AC_active = 8.5 * AC_active_cyto_mem
!F Vmax_PKA_activates_Raf = kcat_PKA_activates_Raf * 0.00166112956810631 * PKA_cyto
!F Vmax_MEK_activates_MAPK = 0.15 * 0.00166112956810631 * MEK_active_cyto
!F Vmax_PDE4_PDE4 = 8.0 * 0.00166112956810631 * PDE4_cyto
!F Vmax_PPase_Raf = kcat_PPase_Raf * 0.00166112956810631 * PP2A_cyto