Simple EGFR model

  • http://bionetgen.org/index.php/Simple_EGFR_model
  • M.L. Blinov, J.R. Faeder, B. Goldstein, W.S. Hlavacek, “A network model of early events in epidermal growth factor receptor signaling that accounts for combinatorial complexity.”, Biosystems, 83(2-3), 136-151, 2006.
%matplotlib inline
from ecell4 import *
NA = 6.02e23  # Avogadro's number (molecules/mol)
f = 1  # Fraction of the cell to simulate
Vo = f * 1.0e-10  # Extracellular volume=1/cell_density (L)
V = f * 3.0e-12  # Cytoplasmic volume (L)

EGF_init = 20 * 1e-9 * NA * Vo  # Initial amount of ligand (20 nM) converted to copies per cell

# Initial amounts of cellular components (copies per cell)
EGFR_init = f * 1.8e5
Grb2_init = f * 1.5e5
Sos1_init = f * 6.2e4

# Rate constants
# Divide by NA*V to convert bimolecular rate constants
# from /M/sec to /(molecule/cell)/sec
kp1 = 9.0e7 / (NA * Vo)  # ligand-monomer binding
km1 = 0.06  # ligand-monomer dissociation
kp2 = 1.0e7 / (NA * V)  # aggregation of bound monomers
km2 = 0.1  # dissociation of bound monomers
kp3 = 0.5  # dimer transphosphorylation
km3 = 4.505  # dimer dephosphorylation
kp4 = 1.5e6 / (NA * V)  # binding of Grb2 to receptor
km4 = 0.05  # dissociation of Grb2 from receptor
kp5 = 1.0e7 / (NA * V)  # binding of Grb2 to Sos1
km5 = 0.06  # dissociation of Grb2 from Sos1
deg = 0.01  # degradation of receptor dimers
with reaction_rules():
  # R1: Ligand-receptor binding
  EGFR(L, CR1) + EGF(R) == EGFR(L^1, CR1).EGF(R^1) | (kp1, km1)

  # R2: Receptor-aggregation
  EGFR(L^_, CR1) + EGFR(L^_, CR1) == EGFR(L^_,CR1^1).EGFR(L^_,CR1^1) | (kp2, km2)

  # R3: Transphosphorylation of EGFR by RTK
  EGFR(CR1^_, Y1068=U) > EGFR(CR1^_, Y1068=P) | kp3

  # R4: Dephosphorylation
  EGFR(Y1068=P) > EGFR(Y1068=U) | km3

  # R5: Grb2 binding to pY1068
  EGFR(Y1068=P) + Grb2(SH2) == EGFR(Y1068=P^1).Grb2(SH2^1) | (kp4, km4)

  # R6: Grb2 binding to Sos1
  Grb2(SH3) + Sos1(PxxP) == Grb2(SH3^1).Sos1(PxxP^1) | (kp5, km5)

  # R7: Receptor dimer internalization/degradation
  (EGF(R^1).EGF(R^2).EGFR(L^1,CR1^3).EGFR(L^2,CR1^3) > ~EmptySet | deg
       | _policy(ReactionRule.STRICT | ReactionRule.DESTROY))

m = get_model(is_netfree=True, effective=True)
y0 = {"EGF(R)": EGF_init, "EGFR(L, CR1, Y1068=U)": EGFR_init, "Grb2(SH2, SH3)": Grb2_init, "Sos1(PxxP)": Sos1_init}
newm = m.expand([Species(serial) for serial in y0.keys()])
print("{} species and {} reactions were generated.".format(len(newm.list_species()), len(newm.reaction_rules())))

for i, sp in enumerate(newm.list_species()):
    print("{}: {}".format(i + 1, sp.serial()))

for i, rr in enumerate(newm.reaction_rules()):
    print("{}: {}".format(i + 1, rr.as_string()))
22 species and 86 reactions were generated.
1: EGF(R)
2: EGF(R^1).EGFR(CR1,L^1,Y1068=P)
3: EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3)
4: EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3^3).Sos1(PxxP^3)
5: EGF(R^1).EGFR(CR1,L^1,Y1068=U)
6: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P).EGF(R^3)
7: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P^4).EGF(R^3).Grb2(SH2^4,SH3)
8: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P^4).EGF(R^3).Grb2(SH2^4,SH3^5).Sos1(PxxP^5)
9: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=U).EGF(R^3)
10: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=P^5).EGF(R^4).Grb2(SH2^5,SH3).Grb2(SH2^3,SH3)
11: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=P^5).EGF(R^4).Grb2(SH2^5,SH3).Grb2(SH2^3,SH3^6).Sos1(PxxP^6)
12: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=P^5).EGF(R^4).Grb2(SH2^5,SH3^6).Sos1(PxxP^6).Grb2(SH2^3,SH3^7).Sos1(PxxP^7)
13: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=U).EGF(R^4).Grb2(SH2^3,SH3)
14: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=U).EGF(R^4).Grb2(SH2^3,SH3^5).Sos1(PxxP^5)
15: EGF(R^1).EGFR(CR1^2,L^1,Y1068=U).EGFR(CR1^2,L^3,Y1068=U).EGF(R^3)
16: EGFR(CR1,L,Y1068=P)
17: EGFR(CR1,L,Y1068=P^1).Grb2(SH2^1,SH3)
18: EGFR(CR1,L,Y1068=P^1).Grb2(SH2^1,SH3^2).Sos1(PxxP^2)
19: EGFR(CR1,L,Y1068=U)
20: Grb2(SH2,SH3)
21: Grb2(SH2,SH3^1).Sos1(PxxP^1)
22: Sos1(PxxP)
1: EGF(R)+EGFR(CR1,L,Y1068=U)>EGF(R^1).EGFR(CR1,L^1,Y1068=U)|1.49502e-06
2: Grb2(SH2,SH3)+Sos1(PxxP)>Grb2(SH2,SH3^1).Sos1(PxxP^1)|5.5371e-06
3: EGF(R^1).EGFR(CR1,L^1,Y1068=U)>EGF(R)+EGFR(CR1,L,Y1068=U)|0.06
4: EGF(R^1).EGFR(CR1,L^1,Y1068=U)+EGF(R^1).EGFR(CR1,L^1,Y1068=U)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=U).EGFR(CR1^2,L^3,Y1068=U).EGF(R^3)|2.76855e-06
5: Grb2(SH2,SH3^1).Sos1(PxxP^1)>Grb2(SH2,SH3)+Sos1(PxxP)|0.06
6: EGF(R^1).EGFR(CR1^2,L^1,Y1068=U).EGFR(CR1^2,L^3,Y1068=U).EGF(R^3)>EGF(R^1).EGFR(CR1,L^1,Y1068=U)+EGF(R^1).EGFR(CR1,L^1,Y1068=U)|0.1
7: EGF(R^1).EGFR(CR1^2,L^1,Y1068=U).EGFR(CR1^2,L^3,Y1068=U).EGF(R^3)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=U).EGF(R^3)|1
8: EGF(R^1).EGFR(CR1^2,L^1,Y1068=U).EGFR(CR1^2,L^3,Y1068=U).EGF(R^3)>|0.01
9: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=U).EGF(R^3)>EGF(R^1).EGFR(CR1,L^1,Y1068=P)+EGF(R^1).EGFR(CR1,L^1,Y1068=U)|0.1
10: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=U).EGF(R^3)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P).EGF(R^3)|0.5
11: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=U).EGF(R^3)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=U).EGFR(CR1^2,L^3,Y1068=U).EGF(R^3)|4.505
12: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=U).EGF(R^3)+Grb2(SH2,SH3^1).Sos1(PxxP^1)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=U).EGF(R^4).Grb2(SH2^3,SH3^5).Sos1(PxxP^5)|8.30565e-07
13: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=U).EGF(R^3)+Grb2(SH2,SH3)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=U).EGF(R^4).Grb2(SH2^3,SH3)|8.30565e-07
14: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=U).EGF(R^3)>|0.01
15: EGF(R^1).EGFR(CR1,L^1,Y1068=P)>EGF(R)+EGFR(CR1,L,Y1068=P)|0.06
16: EGF(R^1).EGFR(CR1,L^1,Y1068=P)+EGF(R^1).EGFR(CR1,L^1,Y1068=P)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P).EGF(R^3)|2.76855e-06
17: EGF(R^1).EGFR(CR1,L^1,Y1068=P)+EGF(R^1).EGFR(CR1,L^1,Y1068=U)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=U).EGF(R^3)|5.5371e-06
18: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P).EGF(R^3)>EGF(R^1).EGFR(CR1,L^1,Y1068=P)+EGF(R^1).EGFR(CR1,L^1,Y1068=P)|0.1
19: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=U).EGF(R^4).Grb2(SH2^3,SH3^5).Sos1(PxxP^5)>EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3^3).Sos1(PxxP^3)+EGF(R^1).EGFR(CR1,L^1,Y1068=U)|0.1
20: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=U).EGF(R^4).Grb2(SH2^3,SH3)>EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3)+EGF(R^1).EGFR(CR1,L^1,Y1068=U)|0.1
21: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=U).EGF(R^4).Grb2(SH2^3,SH3^5).Sos1(PxxP^5)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P^4).EGF(R^3).Grb2(SH2^4,SH3^5).Sos1(PxxP^5)|0.5
22: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=U).EGF(R^4).Grb2(SH2^3,SH3)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P^4).EGF(R^3).Grb2(SH2^4,SH3)|0.5
23: EGF(R^1).EGFR(CR1,L^1,Y1068=P)>EGF(R^1).EGFR(CR1,L^1,Y1068=U)|4.505
24: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P).EGF(R^3)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=U).EGF(R^3)|9.01
25: EGF(R^1).EGFR(CR1,L^1,Y1068=P)+Grb2(SH2,SH3^1).Sos1(PxxP^1)>EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3^3).Sos1(PxxP^3)|8.30565e-07
26: EGF(R^1).EGFR(CR1,L^1,Y1068=P)+Grb2(SH2,SH3)>EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3)|8.30565e-07
27: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P).EGF(R^3)+Grb2(SH2,SH3^1).Sos1(PxxP^1)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P^4).EGF(R^3).Grb2(SH2^4,SH3^5).Sos1(PxxP^5)|1.66113e-06
28: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P).EGF(R^3)+Grb2(SH2,SH3)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P^4).EGF(R^3).Grb2(SH2^4,SH3)|1.66113e-06
29: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=U).EGF(R^4).Grb2(SH2^3,SH3^5).Sos1(PxxP^5)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=U).EGF(R^3)+Grb2(SH2,SH3^1).Sos1(PxxP^1)|0.05
30: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=U).EGF(R^4).Grb2(SH2^3,SH3)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=U).EGF(R^3)+Grb2(SH2,SH3)|0.05
31: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=U).EGF(R^4).Grb2(SH2^3,SH3)+Sos1(PxxP)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=U).EGF(R^4).Grb2(SH2^3,SH3^5).Sos1(PxxP^5)|5.5371e-06
32: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=U).EGF(R^4).Grb2(SH2^3,SH3^5).Sos1(PxxP^5)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=U).EGF(R^4).Grb2(SH2^3,SH3)+Sos1(PxxP)|0.06
33: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P).EGF(R^3)>|0.01
34: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=U).EGF(R^4).Grb2(SH2^3,SH3^5).Sos1(PxxP^5)>|0.01
35: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=U).EGF(R^4).Grb2(SH2^3,SH3)>|0.01
36: EGF(R)+EGFR(CR1,L,Y1068=P)>EGF(R^1).EGFR(CR1,L^1,Y1068=P)|1.49502e-06
37: EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3^3).Sos1(PxxP^3)>EGF(R)+EGFR(CR1,L,Y1068=P^1).Grb2(SH2^1,SH3^2).Sos1(PxxP^2)|0.06
38: EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3)>EGF(R)+EGFR(CR1,L,Y1068=P^1).Grb2(SH2^1,SH3)|0.06
39: EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3^3).Sos1(PxxP^3)+EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3^3).Sos1(PxxP^3)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=P^5).EGF(R^4).Grb2(SH2^5,SH3^6).Sos1(PxxP^6).Grb2(SH2^3,SH3^7).Sos1(PxxP^7)|2.76855e-06
40: EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3)+EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3^3).Sos1(PxxP^3)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=P^5).EGF(R^4).Grb2(SH2^5,SH3).Grb2(SH2^3,SH3^6).Sos1(PxxP^6)|5.5371e-06
41: EGF(R^1).EGFR(CR1,L^1,Y1068=P)+EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3^3).Sos1(PxxP^3)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P^4).EGF(R^3).Grb2(SH2^4,SH3^5).Sos1(PxxP^5)|5.5371e-06
42: EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3^3).Sos1(PxxP^3)+EGF(R^1).EGFR(CR1,L^1,Y1068=U)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=U).EGF(R^4).Grb2(SH2^3,SH3^5).Sos1(PxxP^5)|5.5371e-06
43: EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3)+EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=P^5).EGF(R^4).Grb2(SH2^5,SH3).Grb2(SH2^3,SH3)|2.76855e-06
44: EGF(R^1).EGFR(CR1,L^1,Y1068=P)+EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P^4).EGF(R^3).Grb2(SH2^4,SH3)|5.5371e-06
45: EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3)+EGF(R^1).EGFR(CR1,L^1,Y1068=U)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=U).EGF(R^4).Grb2(SH2^3,SH3)|5.5371e-06
46: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P^4).EGF(R^3).Grb2(SH2^4,SH3^5).Sos1(PxxP^5)>EGF(R^1).EGFR(CR1,L^1,Y1068=P)+EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3^3).Sos1(PxxP^3)|0.1
47: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P^4).EGF(R^3).Grb2(SH2^4,SH3)>EGF(R^1).EGFR(CR1,L^1,Y1068=P)+EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3)|0.1
48: EGFR(CR1,L,Y1068=P)>EGFR(CR1,L,Y1068=U)|4.505
49: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P^4).EGF(R^3).Grb2(SH2^4,SH3^5).Sos1(PxxP^5)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=U).EGF(R^4).Grb2(SH2^3,SH3^5).Sos1(PxxP^5)|4.505
50: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P^4).EGF(R^3).Grb2(SH2^4,SH3)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=U).EGF(R^4).Grb2(SH2^3,SH3)|4.505
51: EGFR(CR1,L,Y1068=P)+Grb2(SH2,SH3^1).Sos1(PxxP^1)>EGFR(CR1,L,Y1068=P^1).Grb2(SH2^1,SH3^2).Sos1(PxxP^2)|8.30565e-07
52: EGFR(CR1,L,Y1068=P)+Grb2(SH2,SH3)>EGFR(CR1,L,Y1068=P^1).Grb2(SH2^1,SH3)|8.30565e-07
53: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P^4).EGF(R^3).Grb2(SH2^4,SH3^5).Sos1(PxxP^5)+Grb2(SH2,SH3^1).Sos1(PxxP^1)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=P^5).EGF(R^4).Grb2(SH2^5,SH3^6).Sos1(PxxP^6).Grb2(SH2^3,SH3^7).Sos1(PxxP^7)|8.30565e-07
54: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P^4).EGF(R^3).Grb2(SH2^4,SH3^5).Sos1(PxxP^5)+Grb2(SH2,SH3)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=P^5).EGF(R^4).Grb2(SH2^5,SH3).Grb2(SH2^3,SH3^6).Sos1(PxxP^6)|8.30565e-07
55: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P^4).EGF(R^3).Grb2(SH2^4,SH3)+Grb2(SH2,SH3^1).Sos1(PxxP^1)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=P^5).EGF(R^4).Grb2(SH2^5,SH3).Grb2(SH2^3,SH3^6).Sos1(PxxP^6)|8.30565e-07
56: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P^4).EGF(R^3).Grb2(SH2^4,SH3)+Grb2(SH2,SH3)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=P^5).EGF(R^4).Grb2(SH2^5,SH3).Grb2(SH2^3,SH3)|8.30565e-07
57: EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3^3).Sos1(PxxP^3)>EGF(R^1).EGFR(CR1,L^1,Y1068=P)+Grb2(SH2,SH3^1).Sos1(PxxP^1)|0.05
58: EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3)>EGF(R^1).EGFR(CR1,L^1,Y1068=P)+Grb2(SH2,SH3)|0.05
59: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P^4).EGF(R^3).Grb2(SH2^4,SH3^5).Sos1(PxxP^5)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P).EGF(R^3)+Grb2(SH2,SH3^1).Sos1(PxxP^1)|0.05
60: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P^4).EGF(R^3).Grb2(SH2^4,SH3)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P).EGF(R^3)+Grb2(SH2,SH3)|0.05
61: EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3)+Sos1(PxxP)>EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3^3).Sos1(PxxP^3)|5.5371e-06
62: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P^4).EGF(R^3).Grb2(SH2^4,SH3)+Sos1(PxxP)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P^4).EGF(R^3).Grb2(SH2^4,SH3^5).Sos1(PxxP^5)|5.5371e-06
63: EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3^3).Sos1(PxxP^3)>EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3)+Sos1(PxxP)|0.06
64: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P^4).EGF(R^3).Grb2(SH2^4,SH3^5).Sos1(PxxP^5)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P^4).EGF(R^3).Grb2(SH2^4,SH3)+Sos1(PxxP)|0.06
65: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P^4).EGF(R^3).Grb2(SH2^4,SH3^5).Sos1(PxxP^5)>|0.01
66: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P^4).EGF(R^3).Grb2(SH2^4,SH3)>|0.01
67: EGF(R)+EGFR(CR1,L,Y1068=P^1).Grb2(SH2^1,SH3^2).Sos1(PxxP^2)>EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3^3).Sos1(PxxP^3)|1.49502e-06
68: EGF(R)+EGFR(CR1,L,Y1068=P^1).Grb2(SH2^1,SH3)>EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3)|1.49502e-06
69: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=P^5).EGF(R^4).Grb2(SH2^5,SH3^6).Sos1(PxxP^6).Grb2(SH2^3,SH3^7).Sos1(PxxP^7)>EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3^3).Sos1(PxxP^3)+EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3^3).Sos1(PxxP^3)|0.1
70: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=P^5).EGF(R^4).Grb2(SH2^5,SH3).Grb2(SH2^3,SH3^6).Sos1(PxxP^6)>EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3)+EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3^3).Sos1(PxxP^3)|0.1
71: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=P^5).EGF(R^4).Grb2(SH2^5,SH3).Grb2(SH2^3,SH3)>EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3)+EGF(R^1).EGFR(CR1,L^1,Y1068=P^2).Grb2(SH2^2,SH3)|0.1
72: EGFR(CR1,L,Y1068=P^1).Grb2(SH2^1,SH3^2).Sos1(PxxP^2)>EGFR(CR1,L,Y1068=P)+Grb2(SH2,SH3^1).Sos1(PxxP^1)|0.05
73: EGFR(CR1,L,Y1068=P^1).Grb2(SH2^1,SH3)>EGFR(CR1,L,Y1068=P)+Grb2(SH2,SH3)|0.05
74: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=P^5).EGF(R^4).Grb2(SH2^5,SH3^6).Sos1(PxxP^6).Grb2(SH2^3,SH3^7).Sos1(PxxP^7)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P^4).EGF(R^3).Grb2(SH2^4,SH3^5).Sos1(PxxP^5)+Grb2(SH2,SH3^1).Sos1(PxxP^1)|0.1
75: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=P^5).EGF(R^4).Grb2(SH2^5,SH3).Grb2(SH2^3,SH3^6).Sos1(PxxP^6)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P^4).EGF(R^3).Grb2(SH2^4,SH3)+Grb2(SH2,SH3^1).Sos1(PxxP^1)|0.05
76: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=P^5).EGF(R^4).Grb2(SH2^5,SH3).Grb2(SH2^3,SH3^6).Sos1(PxxP^6)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P^4).EGF(R^3).Grb2(SH2^4,SH3^5).Sos1(PxxP^5)+Grb2(SH2,SH3)|0.05
77: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=P^5).EGF(R^4).Grb2(SH2^5,SH3).Grb2(SH2^3,SH3)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P).EGFR(CR1^2,L^3,Y1068=P^4).EGF(R^3).Grb2(SH2^4,SH3)+Grb2(SH2,SH3)|0.1
78: EGFR(CR1,L,Y1068=P^1).Grb2(SH2^1,SH3)+Sos1(PxxP)>EGFR(CR1,L,Y1068=P^1).Grb2(SH2^1,SH3^2).Sos1(PxxP^2)|5.5371e-06
79: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=P^5).EGF(R^4).Grb2(SH2^5,SH3).Grb2(SH2^3,SH3^6).Sos1(PxxP^6)+Sos1(PxxP)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=P^5).EGF(R^4).Grb2(SH2^5,SH3^6).Sos1(PxxP^6).Grb2(SH2^3,SH3^7).Sos1(PxxP^7)|5.5371e-06
80: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=P^5).EGF(R^4).Grb2(SH2^5,SH3).Grb2(SH2^3,SH3)+Sos1(PxxP)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=P^5).EGF(R^4).Grb2(SH2^5,SH3).Grb2(SH2^3,SH3^6).Sos1(PxxP^6)|1.10742e-05
81: EGFR(CR1,L,Y1068=P^1).Grb2(SH2^1,SH3^2).Sos1(PxxP^2)>EGFR(CR1,L,Y1068=P^1).Grb2(SH2^1,SH3)+Sos1(PxxP)|0.06
82: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=P^5).EGF(R^4).Grb2(SH2^5,SH3^6).Sos1(PxxP^6).Grb2(SH2^3,SH3^7).Sos1(PxxP^7)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=P^5).EGF(R^4).Grb2(SH2^5,SH3).Grb2(SH2^3,SH3^6).Sos1(PxxP^6)+Sos1(PxxP)|0.12
83: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=P^5).EGF(R^4).Grb2(SH2^5,SH3).Grb2(SH2^3,SH3^6).Sos1(PxxP^6)>EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=P^5).EGF(R^4).Grb2(SH2^5,SH3).Grb2(SH2^3,SH3)+Sos1(PxxP)|0.06
84: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=P^5).EGF(R^4).Grb2(SH2^5,SH3^6).Sos1(PxxP^6).Grb2(SH2^3,SH3^7).Sos1(PxxP^7)>|0.01
85: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=P^5).EGF(R^4).Grb2(SH2^5,SH3).Grb2(SH2^3,SH3^6).Sos1(PxxP^6)>|0.01
86: EGF(R^1).EGFR(CR1^2,L^1,Y1068=P^3).EGFR(CR1^2,L^4,Y1068=P^5).EGF(R^4).Grb2(SH2^5,SH3).Grb2(SH2^3,SH3)>|0.01
species_list = ["EGFR",
                "EGF(R)",
                "EGFR(CR1^_)",
                "EGFR(Y1068=P^_0)",
                "Grb2(SH2, SH3^1).Sos1(PxxP^1)",
                "EGFR(Y1068^1).Grb2(SH2^1, SH3^2).Sos1(PxxP^2)"]
run_simulation(120, model=newm, y0=y0, species_list=species_list,
               opt_kwargs={'interactive': True, 'to_png': True})