def setUp(self):
Monomer('A', ['a'])
Monomer('B', ['b'])
Parameter('ksynthA', 100)
Parameter('ksynthB', 100)
Parameter('kbindAB', 100)
Parameter('A_init', 0)
Parameter('B_init', 0)
Initial(A(a=None), A_init)
Initial(B(b=None), B_init)
Observable("A_free", A(a=None))
Observable("B_free", B(b=None))
Observable("AB_complex", A(a=1) % B(b=1))
Rule('A_synth', None >> A(a=None), ksynthA)
Rule('B_synth', None >> B(b=None), ksynthB)
Rule('AB_bind', A(a=None) + B(b=None) >> A(a=1) % B(b=1), kbindAB)
self.model = model
# This timespan is chosen to be enough to trigger a Jacobian evaluation
# on the various solvers.
self.time = np.linspace(0, 1)
self.solver = Solver(self.model, self.time, integrator='vode')
def setUp(self):
Monomer('A', ['a'])
Monomer('B', ['b'])
Parameter('ksynthA', 100)
Parameter('ksynthB', 100)
Parameter('kbindAB', 100)
Parameter('A_init', 0)
Parameter('B_init', 0)
Initial(A(a=None), A_init)
Initial(B(b=None), B_init)
Observable("A_free", A(a=None))
Observable("B_free", B(b=None))
Observable("AB_complex", A(a=1) % B(b=1))
Rule('A_synth', None >> A(a=None), ksynthA)
Rule('B_synth', None >> B(b=None), ksynthB)
Rule('AB_bind', A(a=None) + B(b=None) >> A(a=1) % B(b=1), kbindAB)
self.model = model
# Convenience shortcut for accessing model monomer objects
self.mon = lambda m: self.model.monomers[m]
# This timespan is chosen to be enough to trigger a Jacobian evaluation
# on the various solvers.
self.time = np.linspace(0, 1)
self.sim = ScipyOdeSimulator(self.model,
tspan=self.time,
integrator='vode')
def test_integrate_with_expression():
"""Ensure a model with Expressions simulates."""
Monomer('s1')
Monomer('s9')
Monomer('s16')
Monomer('s20')
# Parameters should be able to contain s(\d+) without error
Parameter('ks0', 2e-5)
Parameter('ka20', 1e5)
Initial(s9(), Parameter('s9_0', 10000))
Observable('s1_obs', s1())
Observable('s9_obs', s9())
Observable('s16_obs', s16())
Observable('s20_obs', s20())
Expression('keff', (ks0 * ka20) / (ka20 + s9_obs))
Rule('R1', None >> s16(), ks0)
Rule('R2', None >> s20(), ks0)
Rule('R3', s16() + s20() >> s16() + s1(), keff)
time = np.linspace(0, 40)
x = odesolve(model, time)
def test_integrate_with_expression():
"""Ensure a model with Expressions simulates."""
Monomer('s1')
Monomer('s9')
Monomer('s16')
Monomer('s20')
# Parameters should be able to contain s(\d+) without error
Parameter('ks0', 2e-5)
Parameter('ka20', 1e5)
Initial(s9(), Parameter('s9_0', 10000))
Observable('s1_obs', s1())
Observable('s9_obs', s9())
Observable('s16_obs', s16())
Observable('s20_obs', s20())
Expression('keff', (ks0 * ka20) / (ka20 + s9_obs))
Rule('R1', None >> s16(), ks0)
Rule('R2', None >> s20(), ks0)
Rule('R3', s16() + s20() >> s16() + s1(), keff)
time = np.linspace(0, 40)
sim = ScipyOdeSimulator(model, tspan=time)
simres = sim.run()
keff_vals = simres.expressions['keff']
assert len(keff_vals) == len(time)
assert np.allclose(keff_vals, 1.8181818181818182e-05)
def test_integrate_with_expression():
"""Ensure a model with Expressions simulates."""
Monomer('s1')
Monomer('s9')
Monomer('s16')
Monomer('s20')
# Parameters should be able to contain s(\d+) without error
Parameter('ks0', 2e-5)
Parameter('ka20', 1e5)
Initial(s9(), Parameter('s9_0', 10000))
Observable('s1_obs', s1())
Observable('s9_obs', s9())
Observable('s16_obs', s16())
Observable('s20_obs', s20())
Expression('keff', (ks0 * ka20) / (ka20 + s9_obs))
Rule('R1', None >> s16(), ks0)
Rule('R2', None >> s20(), ks0)
Rule('R3', s16() + s20() >> s16() + s1(), keff)
time = np.linspace(0, 40)
solver = Solver(model, time)
solver.run()
assert solver.yexpr_view.shape == (len(time),
len(model.expressions_dynamic()))
assert solver.yobs_view.shape == (len(time), len(model.observables))
def _get_gk_model():
SelfExporter.do_export = True
Model()
Monomer('DUSP6', ['mapk1'])
Monomer('MAP2K1', ['mapk1'])
Monomer('MAPK1', ['phospho', 'map2k1', 'dusp6'], {'phospho': ['u', 'p']})
Parameter('kf_mm_bind_1', 1e-06)
Parameter('kr_mm_bind_1', 0.001)
Parameter('kc_mm_phos_1', 0.001)
Parameter('kf_dm_bind_1', 1e-06)
Parameter('kr_dm_bind_1', 0.001)
Parameter('kc_dm_dephos_1', 0.001)
Parameter('DUSP6_0', 100.0)
Parameter('MAP2K1_0', 100.0)
Parameter('MAPK1_0', 100.0)
Rule('MAP2K1_phospho_bind_MAPK1_phospho_1', MAP2K1(mapk1=None) + \
MAPK1(phospho='u', map2k1=None) >>
MAP2K1(mapk1=1) % MAPK1(phospho='u', map2k1=1), kf_mm_bind_1)
Rule('MAP2K1_phospho_MAPK1_phospho_1', MAP2K1(mapk1=1) % \
MAPK1(phospho='u', map2k1=1) >>
MAP2K1(mapk1=None) + MAPK1(phospho='p', map2k1=None), kc_mm_phos_1)
Rule(
'MAP2K1_dissoc_MAPK1',
MAP2K1(mapk1=1) % MAPK1(map2k1=1) >>
MAP2K1(mapk1=None) + MAPK1(map2k1=None), kr_mm_bind_1)
Rule(
'DUSP6_dephos_bind_MAPK1_phospho_1',
DUSP6(mapk1=None) + MAPK1(phospho='p', dusp6=None) >>
DUSP6(mapk1=1) % MAPK1(phospho='p', dusp6=1), kf_dm_bind_1)
Rule(
'DUSP6_dephos_MAPK1_phospho_1',
DUSP6(mapk1=1) % MAPK1(phospho='p', dusp6=1) >>
DUSP6(mapk1=None) + MAPK1(phospho='u', dusp6=None), kc_dm_dephos_1)
Rule(
'DUSP6_dissoc_MAPK1',
DUSP6(mapk1=1) % MAPK1(dusp6=1) >>
DUSP6(mapk1=None) + MAPK1(dusp6=None), kr_dm_bind_1)
Initial(DUSP6(mapk1=None), DUSP6_0)
Initial(MAP2K1(mapk1=None), MAP2K1_0)
Initial(MAPK1(phospho='u', map2k1=None, dusp6=None), MAPK1_0)
SelfExporter.do_export = False
return model
def add_gf_bolus(model, name: str, created_monomers: List[str]):
bolus = Monomer(f'{name}_ext')
Initial(bolus(), Parameter(f'{name}_0', 0.0), fixed=True)
for created_monomer in created_monomers:
koff = Parameter(f'{name}_{created_monomer}_koff', 0.1)
kd = Parameter(f'{name}_{created_monomer}_kd', 1.0)
kon = Expression(f'{name}_{created_monomer}_kon', kd * koff)
Rule(f'{name}_ext_to_{created_monomer}',
bolus() | model.monomers[created_monomer](inh=None), kon, koff)
from pysb import Model, Monomer, Parameter, Compartment, Rule, Initial, Observable
Model()
Compartment('compartment')
Monomer('A_')
Monomer('B_')
Parameter('a0', 1.0)
Parameter('b0', 1.0)
Parameter('k1', 0.0)
Parameter('k2', 0.0)
Rule('conversion', A_()**compartment | B_()**compartment, k1, k2)
Initial(A_()**compartment, a0)
Initial(B_()**compartment, b0)
Observable("A", A_())
Observable("B", B_())
Ea0_RR,
energy=True)
#RAF and RAFi binding
EnergyPattern('ep_RI', R(i=1) % I(r=1), Gf_RI)
EnergyPattern('ep_RRI', R(r=1, i=None) % R(r=1, i=2) % I(r=2), f_Gf)
EnergyPattern('ep_IRRI',
I(r=3) % R(r=1, i=3) % R(r=1, i=2) % I(r=2),
Expression('fg_G', f_Gf + g_Gf))
Rule('RAF_binds_RAFi',
R(i=None) + I(r=None) | R(i=1) % I(r=1),
phi,
Ea0_RI,
energy=True)
#Initial concentrations, mol/L
Parameter('R_0', 0.01)
Parameter('I_0', 0)
#Set initial concentrations
Initial(R(r=None, i=None), R_0)
Initial(I(r=None), I_0)
#Observables (all possible R and I combination independent of A)
Observable('R_obs', R(r=None, i=None))
Observable('I_obs', I(r=None))
Observable('RR_obs', R(r=1, i=None) % R(r=1, i=None))
Observable('RI_obs', R(r=None, i=1) % I(r=1))
Observable('RRI_obs', R(r=1, i=None) % R(r=1, i=2) % I(r=2))
Observable('IRRI_obs', I(r=2) % R(r=1, i=2) % R(r=1, i=3) % I(r=3))
# =============================================================================
Monomer('IFN_alpha2', ['r1', 'r2'])
Monomer('IFNAR1', ['re', 'ri', 'loc'], {'loc': ['in', 'out']})
Monomer('IFNAR2', ['re', 'ri', 'loc'], {'loc': ['in', 'out']})
Monomer('STAT', ['j', 'loc', 'fdbk'], {'j': ['U', 'P'], 'loc': ['Cyt', 'Nuc']})
Monomer('SOCSmRNA', ['loc', 'reg'], {'loc': ['Nuc', 'Cyt']})
Monomer('SOCS', ['site'])
Monomer('R2USP18', ['re', 'ri', 'loc'], {'loc': ['in', 'out']})
# =============================================================================
# # Seed Species
# =============================================================================
Initial(IFN_alpha2(r1=None, r2=None), Ia)
Initial(IFNAR1(re=None, ri=None, loc='out'), R1)
Parameter('fracUSP18', 0) # 0.6 is reasonable when USP18 turned on
Expression('R2_0', (1 - fracUSP18) * R2)
Expression('R2USP18_0', fracUSP18 * R2)
Initial(IFNAR2(re=None, ri=None, loc='out'), R2_0)
Initial(R2USP18(re=None, ri=None, loc='out'), R2USP18_0)
Initial(STAT(j='U', loc='Cyt', fdbk=None), S)
# =============================================================================
# # Observables
# Use 'WILD' for ?, use 'ANY' for +
# =============================================================================
Rule('PhysicalInteractionRule_2', prot(dna=None, dw=2, loc='cyt', met=None, name='lacZ', prot=None, rna=None, up=None) % prot(dna=None, dw=None, loc='cyt', met=None, name='lacZ', prot=None, rna=None, up=2) + prot(dna=None, dw=1, loc='cyt', met=None, name='lacZ', prot=None, rna=None, up=None) % prot(dna=None, dw=None, loc='cyt', met=None, name='lacZ', prot=None, rna=None, up=1) | prot(dna=None, dw=1, loc='cyt', met=None, name='lacZ', prot=None, rna=None, up=4) % prot(dna=None, dw=2, loc='cyt', met=None, name='lacZ', prot=None, rna=None, up=1) % prot(dna=None, dw=3, loc='cyt', met=None, name='lacZ', prot=None, rna=None, up=2) % prot(dna=None, dw=4, loc='cyt', met=None, name='lacZ', prot=None, rna=None, up=3), fwd_PhysicalInteractionRule_2, rvs_PhysicalInteractionRule_2)
Rule('PhysicalInteractionRule_3', prot(dna=None, dw=None, loc='cyt', met=None, name='lacA', prot=None, rna=None, up=None) + prot(dna=None, dw=None, loc='cyt', met=None, name='lacA', prot=None, rna=None, up=None) | prot(dna=None, dw=1, loc='cyt', met=None, name='lacA', prot=None, rna=None, up=None) % prot(dna=None, dw=None, loc='cyt', met=None, name='lacA', prot=None, rna=None, up=1), fwd_PhysicalInteractionRule_3, rvs_PhysicalInteractionRule_3)
Rule('PhysicalInteractionRule_4', prot(dna=None, dw=None, loc='cyt', met=None, name='lacA', prot=None, rna=None, up=None) + prot(dna=None, dw=1, loc='cyt', met=None, name='lacA', prot=None, rna=None, up=None) % prot(dna=None, dw=None, loc='cyt', met=None, name='lacA', prot=None, rna=None, up=1) | prot(dna=None, dw=1, loc='cyt', met=None, name='lacA', prot=None, rna=None, up=3) % prot(dna=None, dw=2, loc='cyt', met=None, name='lacA', prot=None, rna=None, up=1) % prot(dna=None, dw=3, loc='cyt', met=None, name='lacA', prot=None, rna=None, up=2), fwd_PhysicalInteractionRule_4, rvs_PhysicalInteractionRule_4)
Rule('PhysicalInteractionRule_5', prot(dna=None, dw=None, loc='cyt', met=None, name='lacI', prot=None, rna=None, up=None) + prot(dna=None, dw=None, loc='cyt', met=None, name='lacI', prot=None, rna=None, up=None) | prot(dna=None, dw=1, loc='cyt', met=None, name='lacI', prot=None, rna=None, up=None) % prot(dna=None, dw=None, loc='cyt', met=None, name='lacI', prot=None, rna=None, up=1), fwd_PhysicalInteractionRule_5, rvs_PhysicalInteractionRule_5)
Rule('RXN0_5363', prot(dna=None, dw=ANY, loc='cyt', met=None, name='lacZ', prot=None, rna=None, up=ANY) + met(name='alpha_lactose', loc='cyt', dna=None, met=None, prot=None, rna=None) | prot(dna=None, dw=ANY, loc='cyt', met=None, name='lacZ', prot=None, rna=None, up=ANY) + met(name='alpha_ALLOLACTOSE', loc='cyt', dna=None, met=None, prot=None, rna=None), fwd_RXN0_5363, rvs_RXN0_5363)
Rule('RXN0_5363_beta', prot(dna=None, dw=ANY, loc='cyt', met=None, name='lacZ', prot=None, rna=None, up=ANY) + met(name='beta_lactose', loc='cyt', dna=None, met=None, prot=None, rna=None) | prot(dna=None, dw=ANY, loc='cyt', met=None, name='lacZ', prot=None, rna=None, up=ANY) + met(name='beta_ALLOLACTOSE', loc='cyt', dna=None, met=None, prot=None, rna=None), fwd_RXN0_5363_beta, rvs_RXN0_5363_beta)
Rule('RXN0_7215', prot(dna=None, dw=None, loc='imem', met=None, name='lacY', prot=None, rna=None, up=None) + met(name='PROTON', loc='per', dna=None, met=None, prot=None, rna=None) + met(name='CPD_3561', loc='per', dna=None, met=None, prot=None, rna=None) | prot(dna=None, dw=None, loc='imem', met=None, name='lacY', prot=None, rna=None, up=None) + met(name='PROTON', loc='cyt', dna=None, met=None, prot=None, rna=None) + met(name='CPD_3561', loc='cyt', dna=None, met=None, prot=None, rna=None), fwd_RXN0_7215, rvs_RXN0_7215)
Rule('RXN0_7217', prot(dna=None, dw=None, loc='imem', met=None, name='lacY', prot=None, rna=None, up=None) + met(name='PROTON', loc='per', dna=None, met=None, prot=None, rna=None) + met(name='CPD_3785', loc='per', dna=None, met=None, prot=None, rna=None) | prot(dna=None, dw=None, loc='imem', met=None, name='lacY', prot=None, rna=None, up=None) + met(name='PROTON', loc='cyt', dna=None, met=None, prot=None, rna=None) + met(name='CPD_3785', loc='cyt', dna=None, met=None, prot=None, rna=None), fwd_RXN0_7217, rvs_RXN0_7217)
Rule('RXN0_7219', prot(dna=None, dw=ANY, loc='cyt', met=None, name='lacZ', prot=None, rna=None, up=ANY) + met(name='CPD_3785', loc='cyt', dna=None, met=None, prot=None, rna=None) + met(name='WATER', loc='cyt', dna=None, met=None, prot=None, rna=None) | prot(dna=None, dw=ANY, loc='cyt', met=None, name='lacZ', prot=None, rna=None, up=ANY) + met(name='beta_GALACTOSE', loc='cyt', dna=None, met=None, prot=None, rna=None) + met(name='D_ARABINOSE', loc='cyt', dna=None, met=None, prot=None, rna=None), fwd_RXN0_7219, rvs_RXN0_7219)
Rule('RXN_17726', prot(dna=None, dw=ANY, loc='cyt', met=None, name='lacZ', prot=None, rna=None, up=ANY) + met(name='CPD_3561', loc='cyt', dna=None, met=None, prot=None, rna=None) + met(name='WATER', loc='cyt', dna=None, met=None, prot=None, rna=None) | prot(dna=None, dw=ANY, loc='cyt', met=None, name='lacZ', prot=None, rna=None, up=ANY) + met(name='beta_GALACTOSE', loc='cyt', dna=None, met=None, prot=None, rna=None) + met(name='Fructofuranose', loc='cyt', dna=None, met=None, prot=None, rna=None), fwd_RXN_17726, rvs_RXN_17726)
Rule('RXN_17755', prot(dna=None, dw=None, loc='imem', met=None, name='lacY', prot=None, rna=None, up=None) + met(name='PROTON', loc='per', dna=None, met=None, prot=None, rna=None) + met(name='CPD_3801', loc='per', dna=None, met=None, prot=None, rna=None) | prot(dna=None, dw=None, loc='imem', met=None, name='lacY', prot=None, rna=None, up=None) + met(name='PROTON', loc='cyt', dna=None, met=None, prot=None, rna=None) + met(name='CPD_3801', loc='cyt', dna=None, met=None, prot=None, rna=None), fwd_RXN_17755, rvs_RXN_17755)
Rule('TRANS_RXN_24', prot(dna=None, dw=None, loc='imem', met=None, name='lacY', prot=None, rna=None, up=None) + met(name='PROTON', loc='per', dna=None, met=None, prot=None, rna=None) + met(name='alpha_lactose', loc='per', dna=None, met=None, prot=None, rna=None) | prot(dna=None, dw=None, loc='imem', met=None, name='lacY', prot=None, rna=None, up=None) + met(name='PROTON', loc='cyt', dna=None, met=None, prot=None, rna=None) + met(name='alpha_lactose', loc='cyt', dna=None, met=None, prot=None, rna=None), fwd_TRANS_RXN_24, rvs_TRANS_RXN_24)
Rule('TRANS_RXN_24_beta', prot(dna=None, dw=None, loc='imem', met=None, name='lacY', prot=None, rna=None, up=None) + met(name='PROTON', loc='per', dna=None, met=None, prot=None, rna=None) + met(name='beta_lactose', loc='per', dna=None, met=None, prot=None, rna=None) | prot(dna=None, dw=None, loc='imem', met=None, name='lacY', prot=None, rna=None, up=None) + met(name='PROTON', loc='cyt', dna=None, met=None, prot=None, rna=None) + met(name='beta_lactose', loc='cyt', dna=None, met=None, prot=None, rna=None), fwd_TRANS_RXN_24_beta, rvs_TRANS_RXN_24_beta)
Rule('TRANS_RXN_94', prot(dna=None, dw=None, loc='imem', met=None, name='lacY', prot=None, rna=None, up=None) + met(name='PROTON', loc='per', dna=None, met=None, prot=None, rna=None) + met(name='MELIBIOSE', loc='per', dna=None, met=None, prot=None, rna=None) | prot(dna=None, dw=None, loc='imem', met=None, name='lacY', prot=None, rna=None, up=None) + met(name='PROTON', loc='cyt', dna=None, met=None, prot=None, rna=None) + met(name='MELIBIOSE', loc='cyt', dna=None, met=None, prot=None, rna=None), fwd_TRANS_RXN_94, rvs_TRANS_RXN_94)
Initial(prot(dna=None, dw=None, loc='cyt', met=None, name='lacA', prot=None, rna=None, up=None), t0_prot_lacA_cyt)
Initial(prot(dna=None, dw=None, loc='cyt', met=None, name='lacI', prot=None, rna=None, up=None), t0_prot_lacI_cyt)
Initial(prot(dna=None, dw=None, loc='cyt', met=None, name='lacZ', prot=None, rna=None, up=None), t0_prot_lacZ_cyt)
Initial(prot(dna=None, dw=1, loc='cyt', met=None, name='lacA', prot=None, rna=None, up=None) % prot(dna=None, dw=2, loc='cyt', met=None, name='lacA', prot=None, rna=None, up=1) % prot(dna=None, dw=None, loc='cyt', met=None, name='lacA', prot=None, rna=None, up=2), t0_cplx_lacAx3_cyt)
Initial(prot(dna=None, dw=1, loc='cyt', met=None, name='lacA', prot=None, rna=None, up=None) % prot(dna=None, dw=None, loc='cyt', met=None, name='lacA', prot=None, rna=None, up=1), t0_cplx_lacAx2_cyt)
Initial(prot(dna=None, dw=1, loc='cyt', met=None, name='lacI', prot=None, rna=None, up=None) % prot(dna=None, dw=None, loc='cyt', met=None, name='lacI', prot=None, rna=None, up=1), t0_cplx_lacIx2_cyt)
Initial(prot(dna=None, dw=1, loc='cyt', met=None, name='lacZ', prot=None, rna=None, up=None) % prot(dna=None, dw=2, loc='cyt', met=None, name='lacZ', prot=None, rna=None, up=1) % prot(dna=None, dw=3, loc='cyt', met=None, name='lacZ', prot=None, rna=None, up=2) % prot(dna=None, dw=None, loc='cyt', met=None, name='lacZ', prot=None, rna=None, up=3), t0_cplx_lacZx4_cyt)
Initial(prot(dna=None, dw=1, loc='cyt', met=None, name='lacZ', prot=None, rna=None, up=None) % prot(dna=None, dw=None, loc='cyt', met=None, name='lacZ', prot=None, rna=None, up=1), t0_cplx_lacZx2_cyt)
Initial(met(name='ACETYL_COA', loc='cyt', dna=None, met=None, prot=None, rna=None), t0_met_ACETYL_COA_cyt)
Initial(met(name='CO_A', loc='cyt', dna=None, met=None, prot=None, rna=None), t0_met_CO_A_cyt)
Initial(met(name='CPD_3561', loc='cyt', dna=None, met=None, prot=None, rna=None), t0_met_CPD_3561_cyt)
Initial(met(name='CPD_3785', loc='cyt', dna=None, met=None, prot=None, rna=None), t0_met_CPD_3785_cyt)
Initial(met(name='CPD_3801', loc='cyt', dna=None, met=None, prot=None, rna=None), t0_met_CPD_3801_cyt)
Initial(met(name='D_ARABINOSE', loc='cyt', dna=None, met=None, prot=None, rna=None), t0_met_D_ARABINOSE_cyt)
Initial(met(name='Fructofuranose', loc='cyt', dna=None, met=None, prot=None, rna=None), t0_met_Fructofuranose_cyt)
Initial(met(name='MELIBIOSE', loc='cyt', dna=None, met=None, prot=None, rna=None), t0_met_MELIBIOSE_cyt)
Rule('synthesis_EGF', None >> EGF(inh=None), EGF_synthesis_rate)
Rule('degradation_EGF', EGF() >> None, EGF_degradation_rate)
Rule('EGF_ext_to_EGF', EGF_ext() | EGF(inh=None), EGF_EGF_kon, EGF_EGF_koff)
Rule('synthesis_EGFR', None >> EGFR(Y1173='u', inh=None), EGFR_synthesis_rate)
Rule('degradation_EGFR', EGFR() >> None, EGFR_degradation_rate)
Rule('EGFR_Y1173_base',
EGFR(Y1173='p') | EGFR(Y1173='u'), EGFR_phosphorylation_Y1173_base_rate,
EGFR_dephosphorylation_Y1173_base_rate)
Rule('synthesis_ERBB2', None >> ERBB2(Y1248='u', inh=None),
ERBB2_synthesis_rate)
Rule('degradation_ERBB2', ERBB2() >> None, ERBB2_degradation_rate)
Rule('ERBB2_Y1248_base',
ERBB2(Y1248='p') | ERBB2(Y1248='u'),
ERBB2_phosphorylation_Y1248_base_rate,
ERBB2_dephosphorylation_Y1248_base_rate)
Rule('EGFR_phosphorylation_Y1173_EGF',
EGFR(Y1173='u') >> EGFR(Y1173='p'), EGFR_phosphorylation_Y1173_EGF_rate)
Rule('ERBB2_phosphorylation_Y1248_EGF',
ERBB2(Y1248='u') >> ERBB2(Y1248='p'),
ERBB2_phosphorylation_Y1248_EGF_rate)
Rule('iEGFR_inhibits_EGFR',
EGFR(inh=None) + iEGFR(target=None) | EGFR(inh=1) % iEGFR(target=1),
iEGFR_EGFR_kon, iEGFR_EGFR_koff)
Initial(EGF(inh=None), EGF_ss)
Initial(EGF_ext(), EGF_0, fixed=True)
Initial(EGFR(Y1173='u', inh=None), EGFR_ss)
Initial(ERBB2(Y1248='u', inh=None), ERBB2_ss)
Initial(iEGFR(target=None), iEGFR_0, fixed=True)
# =============================================================================
# # Molecules
# =============================================================================
Monomer('IFN_alpha2', ['r1', 'r2'])
Monomer('IFNAR1', ['re', 'ri', 'loc'], {'loc': ['in', 'out']})
Monomer('IFNAR2', ['re', 'ri', 'rs', 'loc'], {'loc': ['in', 'out']})
Monomer('STAT', ['j', 'loc', 'fdbk'], {'j': ['U', 'P'], 'loc': ['Cyt', 'Nuc']})
Monomer('SOCSmRNA', ['loc', 'reg'], {'loc': ['Nuc', 'Cyt']})
Monomer('SOCS', ['site'])
# =============================================================================
# # Seed Species
# =============================================================================
Initial(IFN_alpha2(r1=None, r2=None), I)
Initial(IFNAR1(re=None, ri=None, loc='out'), R1)
Initial(IFNAR2(re=None, ri=None, rs=None, loc='out'), R2)
Initial(STAT(j='U', loc='Cyt', fdbk=None), S)
# =============================================================================
# # Observables
# Use 'WILD' for ?, use 'ANY' for +
# =============================================================================
Observable('Free_Ia', IFN_alpha2(r1=None, r2=None))
Observable('Free_R1', IFNAR1(re=None, ri=None, loc='out'))
Observable('Free_R2', IFNAR2(re=None, ri=None, rs=None, loc='out'))
Observable('R1Ia',
| cplx(name='GALACTOACETYLTRAN_CPLX',
loc='cyt',
dna=None,
met=None,
prot=None,
rna=None) + met(name='_6_Acetyl_beta_D_Galactose',
loc='cyt',
dna=None,
met=None,
prot=None,
rna=None) +
met(name='CO_A', loc='cyt', dna=None, met=None, prot=None, rna=None),
fwd_GALACTOACETYLTRAN_RXN_galactose, rvs_GALACTOACETYLTRAN_RXN_galactose)
Initial(
met(name='ACETYL_COA', loc='cyt', dna=None, met=None, prot=None, rna=None),
t0_met_ACETYL_COA_cyt)
Initial(met(name='CO_A', loc='cyt', dna=None, met=None, prot=None, rna=None),
t0_met_CO_A_cyt)
Initial(
met(name='CPD_3561', loc='cyt', dna=None, met=None, prot=None, rna=None),
t0_met_CPD_3561_cyt)
Initial(
met(name='CPD_3785', loc='cyt', dna=None, met=None, prot=None, rna=None),
t0_met_CPD_3785_cyt)
Initial(
met(name='CPD_3801', loc='cyt', dna=None, met=None, prot=None, rna=None),
t0_met_CPD_3801_cyt)
Initial(
met(name='D_ARABINOSE', loc='cyt', dna=None, met=None, prot=None,
rna=None), t0_met_D_ARABINOSE_cyt)
from pysb import ANY, WILD, Model, Monomer, Parameter, Expression, Initial, Observable, Rule
from pysb.macros import *
Model()
###################################################################################################
# DNA
Monomer('DNA_rpoA', ['type'], {'type': ['P1', 'RBS', 'CDS', 'T1']})
Initial(DNA_rpoA(type = 'P1'), Parameter('t0_DNA_rpoA_P1', 1))
Initial(DNA_rpoA(type = 'RBS'), Parameter('t0_DNA_rpoA_RBS', 1))
Initial(DNA_rpoA(type = 'CDS'), Parameter('t0_DNA_rpoA_CDS', 1))
Initial(DNA_rpoA(type = 'T1'), Parameter('t0_DNA_rpoA_T1', 1))
Monomer('DNA_rpoB', ['type'], {'type': ['P1', 'RBS', 'CDS', 'T1']})
Initial(DNA_rpoB(type = 'P1'), Parameter('t0_DNA_rpoB_P1', 1))
Initial(DNA_rpoB(type = 'RBS'), Parameter('t0_DNA_rpoB_RBS', 1))
Initial(DNA_rpoB(type = 'CDS'), Parameter('t0_DNA_rpoB_CDS', 1))
Monomer('DNA_rpoC', ['type'], {'type': ['RBS', 'CDS', 'T1']})
Initial(DNA_rpoC(type = 'RBS'), Parameter('t0_DNA_rpoC_RBS', 1))
Initial(DNA_rpoC(type = 'CDS'), Parameter('t0_DNA_rpoC_CDS', 1))
Initial(DNA_rpoC(type = 'T1'), Parameter('t0_DNA_rpoC_T1', 1))
Monomer('DNA_rpoD', ['type'], {'type': ['P1', 'RBS', 'CDS', 'T1']})
Initial(DNA_rpoD(type = 'P1'), Parameter('t0_DNA_rpoD_P1', 1))
Initial(DNA_rpoD(type = 'RBS'), Parameter('t0_DNA_rpoD_RBS', 1))
Initial(DNA_rpoD(type = 'CDS'), Parameter('t0_DNA_rpoD_CDS', 1))
Initial(DNA_rpoD(type = 'T1'), Parameter('t0_DNA_rpoD_T1', 1))
Monomer('DNA_rpoE', ['type'], {'type': ['P1', 'RBS', 'CDS', 'T1']})
Initial(DNA_rpoE(type = 'P1'), Parameter('t0_DNA_rpoE_P1', 1))
Monomer('A', ['B', 'C'])
Monomer('B', ['A', 'D'])
Monomer('C', ['A'])
Monomer('D', ['B'])
Parameter('inhibition_0_A_inhibitor_B_inh_target_2kf_0', 1.5e-05)
Parameter('inhibition_0_A_inhibitor_B_inh_target_1kr_0', 0.00012)
Parameter('inhibition_0_A_inhibitor_C_inh_target_2kf_0', 4e-05)
Parameter('inhibition_0_A_inhibitor_C_inh_target_1kr_0', 7e-06)
Parameter('inhibition_0_B_inhibitor_D_inh_target_2kf_0', 1e-05)
Parameter('inhibition_0_B_inhibitor_D_inh_target_1kr_0', 6e-06)
Parameter('A_0', 200000.0)
Parameter('B_0', 50000.0)
Parameter('C_0', 20000.0)
Parameter('D_0', 10000.0)
Observable('A_obs', A())
Observable('B_obs', B())
Observable('C_obs', C())
Observable('D_obs', D())
Rule('inhibition_0_A_inhibitor_B_inh_target', A(B=None, C=None) + B(A=None, D=None) | A(B=1, C=None) % B(A=1, D=None), inhibition_0_A_inhibitor_B_inh_target_2kf_0, inhibition_0_A_inhibitor_B_inh_target_1kr_0)
Rule('inhibition_0_A_inhibitor_C_inh_target', A(B=None, C=None) + C(A=None) | A(B=None, C=1) % C(A=1), inhibition_0_A_inhibitor_C_inh_target_2kf_0, inhibition_0_A_inhibitor_C_inh_target_1kr_0)
Rule('inhibition_0_B_inhibitor_D_inh_target', B(A=None, D=None) + D(B=None) | B(A=None, D=1) % D(B=1), inhibition_0_B_inhibitor_D_inh_target_2kf_0, inhibition_0_B_inhibitor_D_inh_target_1kr_0)
Initial(A(B=None, C=None), A_0)
Initial(B(A=None, D=None), B_0)
Initial(C(A=None), C_0)
Initial(D(B=None), D_0)
Observable('AB_complex',A(B=1)%B(A=1))
Rule(
'MEK_p1_p1_phosphorylation_ERK_0',
MEK(RAF=None, p1_site='p', ERK=None) +
ERK(p1_site='u', p70S6K=None, IRS1=None, GSK3=None, MEK=None) <>
MEK(RAF=None, p1_site='p', ERK=1) %
ERK(p1_site='u', p70S6K=None, IRS1=None, GSK3=None, MEK=1),
MEK_p1_p1_phosphorylation_ERK_0_2kf, MEK_p1_p1_phosphorylation_ERK_0_1kr)
Rule(
'MEK_p1_p1_phosphorylation_ERK_1',
MEK(RAF=None, p1_site='p', ERK=1) %
ERK(p1_site='u', p70S6K=None, IRS1=None, GSK3=None, MEK=1) >>
MEK(RAF=None, p1_site='p', ERK=None) +
ERK(p1_site='p', p70S6K=None, IRS1=None, GSK3=None, MEK=None),
MEK_p1_p1_phosphorylation_ERK_1_1kc)
Initial(RAF(state='I', MEK=None), RAF_0_0)
Initial(RAF(state='A', MEK=None), RAF_1_0)
Initial(TGFa(EGFR=None), TGFa_0_0)
Initial(IGF1R(state='A', IGF1=None), IGF1R_0_0)
Initial(IGF1R(state='I', IGF1=None), IGF1R_1_0)
Initial(IGF1(IGF1R=None), IGF1_0_0)
Initial(PI3K(state='I', AKT=None), PI3K_0_0)
Initial(PI3K(state='A', AKT=None), PI3K_1_0)
Initial(p70S6K(AKT=None, p1_site='u', ERK=None), p70S6K_0_0)
Initial(p70S6K(AKT=None, p1_site='p', ERK=None), p70S6K_1_0)
Initial(EGFR(state='A', TGFa=None), EGFR_0_0)
Initial(EGFR(state='I', TGFa=None), EGFR_1_0)
Initial(IRS1(AKT=None, p1_site='u', ERK=None), IRS1_0_0)
Initial(IRS1(AKT=None, p1_site='p', ERK=None), IRS1_1_0)
Initial(MEK(RAF=None, p1_site='u', ERK=None), MEK_0_0)
Initial(MEK(RAF=None, p1_site='p', ERK=None), MEK_1_0)
EnergyPattern('ep_IRRI',
I(r=3) % R(r=1, i=3) % R(r=1, i=2) % I(r=2),
Expression('fg_G', f_Gf + g_Gf))
Rule('RAF_binds_RAFi',
R(i=None) + I(r=None) | R(i=1) % I(r=1),
phi,
Ea0_RI,
energy=True)
#Initial concentrations, mol/L
Parameter('A_0', 0.1)
Parameter('R_0', 0.01)
Parameter('I_0', 0)
#Set initial concentrations
Initial(A(r=None), A_0)
Initial(R(a=None, r=None, i=None), R_0)
Initial(I(r=None), I_0)
#Observables
#not inhibited RAF monomer
Observable('RAF_monomer_not_I_bound_obs', R(r=None, i=None))
#not inhibited RAF promoter in dimer
Observable('RAF_dimer_not_I_bound_obs', R(r=1, i=None) % R(r=1))
#not inhibited RAF monomers and promoter in dimer
Observable('RAF_monomer_and_dimer_not_I_bound_obs',
R(r=None, i=None) + R(r=1, i=None) % R(r=1))
## RAS binding RAF
#Parameter('G_AR',1 / RT)
#Parameter('r_G', 1 / RT)
Rule('translation', s() >> s() + p(b=None), k_p) # Translation reaction
Rule('splicing', u() >> s(), beta) # splicing reaction
Rule('death_s', s() >> None, d_s) # Degradation reactions
Rule('death_p', p(b=None) >> None, d_p)
Rule('g_bind',
g(b=None) + p(b=None) | g(b=1) % p(b=1), b_f,
b_r) # gene-protein binding reaction
# ------------------------------------------------
# initial conditions
Parameter('g_0', 1)
Parameter('u_0', 0)
Parameter('s_0', 0)
Parameter('p_0', 0)
Initial(g(b=None), g_0)
Initial(u, u_0)
Initial(s, s_0)
Initial(p(b=None), p_0)
# Observables
Observable('o_g_0', g(b=None))
Observable('o_g_1', g(b=1) % p(b=1))
Observable('o_u', u)
Observable('o_s', s)
Observable('o_p', p(b=None))
u'PPM1D_deactivates_TP53_activity',
PPM1D(activity=u'active') + TP53(activity=u'active') >>
PPM1D(activity=u'active') + TP53(activity=u'inactive'), kf_pt_act_1)
Rule(
u'MDM2_deactivates_TP53_activity',
MDM2(activity=u'active') + TP53(activity=u'active') >>
MDM2(activity=u'active') + TP53(activity=u'inactive'), kf_mt_act_1)
Rule(
u'HIPK2_deactivates_PPM1D_activity',
HIPK2() + PPM1D(activity=u'active') >>
HIPK2() + PPM1D(activity=u'inactive'), kf_hp_act_1)
Rule(u'ARF_deactivates_MDM2_activity',
ARF() + MDM2(activity=u'active') >> ARF() + MDM2(activity=u'inactive'),
kf_am_act_1)
Initial(PPM1D(activity=u'inactive'), PPM1D_0)
Initial(TP53(activity=u'inactive'), TP53_0)
Initial(HIPK2(), HIPK2_0)
Initial(ATR(activity=u'inactive'), ATR_0)
Initial(ARF(), ARF_0)
Initial(MDM2(activity=u'inactive'), MDM2_0)
Initial(ATR(activity=u'active'), ATRa_0)
Annotation(PPM1D, u'http://identifiers.org/hgnc/HGNC:9277', u'is')
Annotation(PPM1D, u'http://identifiers.org/uniprot/O15297', u'is')
Annotation(TP53, u'http://identifiers.org/hgnc/HGNC:11998', u'is')
Annotation(TP53, u'http://identifiers.org/uniprot/P04637', u'is')
Annotation(HIPK2, u'http://identifiers.org/uniprot/Q9H2X6', u'is')
Annotation(HIPK2, u'http://identifiers.org/hgnc/HGNC:14402', u'is')
Annotation(ATR, u'http://identifiers.org/uniprot/Q13535', u'is')
Annotation(ATR, u'http://identifiers.org/hgnc/HGNC:882', u'is')
pore_transport_complex_BakA_4_SmacM_kf,
pore_transport_complex_BakA_4_SmacM_kr)
Rule(
'pore_transport_dissociate_BakA_4_SmacC',
MatchOnce(
Bak(bf=5, s1=4, s2=1, state='A') % Bak(bf=None, s1=1, s2=2, state='A')
% Bak(bf=None, s1=2, s2=3, state='A') %
Bak(bf=None, s1=3, s2=4, state='A') % Smac(bf=5, state='M')) >>
MatchOnce(
Bak(bf=None, s1=4, s2=1, state='A') %
Bak(bf=None, s1=1, s2=2, state='A') %
Bak(bf=None, s1=2, s2=3, state='A') %
Bak(bf=None, s1=3, s2=4, state='A')) + Smac(bf=None, state='C'),
pore_transport_dissociate_BakA_4_SmacC_kc)
Initial(L(bf=None), L_0)
Initial(R(bf=None), R_0)
Initial(flip(bf=None), Flip_0)
Initial(C8(bf=None, state='pro'), C8_0)
Initial(BAR(bf=None), BAR_0)
Initial(Apaf(bf=None, state='I'), Apaf_0)
Initial(C3(bf=None, state='pro'), C3_0)
Initial(C6(bf=None, state='pro'), C6_0)
Initial(C9(bf=None), C9_0)
Initial(PARP(bf=None, state='U'), PARP_0)
Initial(XIAP(bf=None), XIAP_0)
Initial(Bid(bf=None, state='U'), Bid_0)
Initial(Bax(bf=None, s1=None, s2=None, state='C'), Bax_0)
Initial(Bak(bf=None, s1=None, s2=None, state='M'), Bak_0)
Initial(Bcl2(bf=None, state='M'), Bcl2_0)
Initial(BclxL(bf=None, state='M'), BclxL_0)
# # Molecules
# =============================================================================
Monomer('IFN_alpha2', ['r1', 'r2'])
Monomer('IFN_beta', ['r1', 'r2'])
Monomer('IFNAR1', ['re', 'ri', 'loc'], {'loc': ['in', 'out']})
Monomer('IFNAR2', ['re', 'ri', 'loc'], {'loc': ['in', 'out']})
Monomer('STAT', ['j', 'loc', 'fdbk'], {'j': ['U', 'P'], 'loc': ['Cyt', 'Nuc']})
Monomer('SOCS', ['site'])
# =============================================================================
# # Seed Species
# =============================================================================
Initial(IFN_alpha2(r1=None, r2=None), Ia)
Initial(IFN_beta(r1=None, r2=None), Ib)
Initial(IFNAR1(re=None, ri=None, loc='out'), R1)
Initial(IFNAR2(re=None, ri=None, loc='out'), R2)
Initial(STAT(j='U', loc='Cyt', fdbk=None), S)
Initial(STAT(j='P', loc='Cyt', fdbk=None), pS)
Initial(SOCS(site=None), Initial_SOCS)
# =============================================================================
# # Observables
# =============================================================================
Observable('Free_Ia', IFN_alpha2(r1=None, r2=None))
Observable('Free_Ib', IFN_beta(r1=None, r2=None))
MAP2K1_phosphorylation_S222_BRAF__S445_p_rate)
Rule('MAP2K2_phosphorylation_S226_RAF1__S338_p',
MAP2K2(S226='u', S222='u') >> MAP2K2(S226='p', S222='p'),
MAP2K2_phosphorylation_S226_RAF1__S338_p_rate)
Rule('MAP2K2_phosphorylation_S226_BRAF__S445_p',
MAP2K2(S226='u', S222='u') >> MAP2K2(S226='p', S222='p'),
MAP2K2_phosphorylation_S226_BRAF__S445_p_rate)
Rule('MAPK1_phosphorylation_Y187_MAP2K1__S218_p__S222_p',
MAPK1(Y187='u', T185='u') >> MAPK1(Y187='p', T185='p'),
MAPK1_phosphorylation_Y187_MAP2K1__S218_p__S222_p_rate)
Rule('MAPK1_phosphorylation_Y187_MAP2K2__S222_p__S226_p',
MAPK1(Y187='u', T185='u') >> MAPK1(Y187='p', T185='p'),
MAPK1_phosphorylation_Y187_MAP2K2__S222_p__S226_p_rate)
Rule('MAPK3_phosphorylation_Y204_MAP2K1__S218_p__S222_p',
MAPK3(T202='u', Y204='u') >> MAPK3(T202='p', Y204='p'),
MAPK3_phosphorylation_Y204_MAP2K1__S218_p__S222_p_rate)
Rule('MAPK3_phosphorylation_Y204_MAP2K2__S222_p__S226_p',
MAPK3(T202='u', Y204='u') >> MAPK3(T202='p', Y204='p'),
MAPK3_phosphorylation_Y204_MAP2K2__S222_p__S226_p_rate)
Initial(EGF(inh=None), EGF_eq)
Initial(EGF_ext(), EGF_0, fixed=True)
Initial(EGFR(Y1173='u', inh=None), EGFR_eq)
Initial(ERBB2(Y1248='u', inh=None), ERBB2_eq)
Initial(RAF1(S338='u', inh=None), RAF1_eq)
Initial(BRAF(S445='u', inh=None), BRAF_eq)
Initial(MAP2K1(S218='u', S222='u', inh=None), MAP2K1_eq)
Initial(MAP2K2(S226='u', S222='u', inh=None), MAP2K2_eq)
Initial(MAPK1(Y187='u', T185='u', inh=None), MAPK1_eq)
Initial(MAPK3(T202='u', Y204='u', inh=None), MAPK3_eq)
Parameter('INPUT_ERBB2_phosphorylation_Y1248_EGF_kcat', 0.0)
Expression('EGF_synthesis_ksyn', EGF_degradation_kdeg*EGF_eq)
Expression('EGF_synthesis_rate', EGF_synthesis_ksyn*INPUT_EGF_eq)
Expression('EGF_degradation_rate', EGF_degradation_kdeg)
Expression('EGF_ss', EGF_synthesis_rate/EGF_degradation_rate)
Expression('EGF_EGF_kon', EGF_EGF_kd*EGF_EGF_koff)
Expression('ERBB2_synthesis_ksyn', ERBB2_degradation_kdeg*ERBB2_eq)
Expression('ERBB2_synthesis_rate', ERBB2_synthesis_ksyn*INPUT_ERBB2_eq)
Expression('ERBB2_degradation_rate', ERBB2_degradation_kdeg)
Expression('ERBB2_ss', ERBB2_synthesis_rate/ERBB2_degradation_rate)
Expression('ERBB2_phosphorylation_Y1248_base_rate', ERBB2_phosphorylation_Y1248_base_kcat*INPUT_ERBB2_phosphorylation_Y1248_base_kcat)
Expression('ERBB2_dephosphorylation_Y1248_base_rate', ERBB2_dephosphorylation_Y1248_base_kcat*INPUT_ERBB2_dephosphorylation_Y1248_base_kcat)
Observable('EGF_obs', EGF(inh=None))
Observable('tEGF', EGF())
Observable('tEGF_ext', EGF_ext())
Observable('tERBB2', ERBB2())
Observable('pERBB2_Y1248', ERBB2(Y1248='p'))
Expression('ERBB2_phosphorylation_Y1248_EGF_rate', EGF_obs*ERBB2_phosphorylation_Y1248_EGF_kcat*INPUT_ERBB2_phosphorylation_Y1248_EGF_kcat)
Rule('EGF_ext_to_EGF', EGF_ext() | EGF(inh=None), EGF_EGF_kon, EGF_EGF_koff)
Rule('ERBB2_Y1248_base', ERBB2(Y1248='p') >> ERBB2(Y1248='u'), ERBB2_dephosphorylation_Y1248_base_rate)
Rule('ERBB2_phosphorylation_Y1248_EGF', ERBB2(Y1248='u') >> ERBB2(Y1248='p'), ERBB2_phosphorylation_Y1248_EGF_rate)
Initial(EGF(inh=None), EGF_ss)
Initial(EGF_ext(), EGF_0, fixed=True)
Initial(ERBB2(Y1248='u', inh=None), ERBB2_ss)
ep_RAF_RAF_mod_RAFi_double_Gf)
EnergyPattern(
'ep_CRAF_CRAF_mod_RAFi_double',
CRAF(raf=1, rafi=2) % CRAF(raf=1, rafi=3) % RAFi(raf=2) % RAFi(raf=3),
ep_RAF_RAF_mod_RAFi_double_Gf)
EnergyPattern('ep_bind_BRAF_MEKphosphou',
BRAF(mek=1) % MEK(phospho='u', raf=1), Gf_bind_BRAF_MEKphosphou)
EnergyPattern('ep_bind_CRAF_MEKphosphou',
CRAF(mek=1) % MEK(phospho='u', raf=1), Gf_bind_CRAF_MEKphosphou)
EnergyPattern('ep_bind_MEKi_MEK', MEK(meki=1) % MEKi(mek=1), Gf_bind_MEKi_MEK)
EnergyPattern('ep_MEKphosphop_MEKi_single',
MEK(meki=1, phospho='p') % MEKi(mek=1), ep_MEKphosphop_MEKi_Gf)
EnergyPattern('ep_SOS1S1134p_GRB2_single',
GRB2(SH3=1) % SOS1(S1134='p', SH3=1), ep_SOS1S1134p_GRB2_Gf)
Initial(RAFi(raf=None), initRAFi, fixed=True)
Initial(MEKi(mek=None), initMEKi, fixed=True)
Initial(EGF(rtk=None), initEGF, fixed=True)
Initial(BRAF(AA600='E', RBD=None, mek=None, raf=None, rafi=None), initBRAF)
Initial(CRAF(RBD=None, mek=None, raf=None, rafi=None), initCRAF)
Initial(RAS(raf=None, sos1=None, state='gdp'), initRAS)
Initial(MEK(Dsite=None, meki=None, phospho='u', raf=None), initMEK)
Initial(ERK(CD=None, phospho='u'), initERK)
Initial(GRB2(SH2=None, SH3=None), initGRB2)
Initial(SOS1(S1134='u', SH3=None, ras=None), initSOS1)
Annotation(RAFi, 'http://identifiers.org/chebi/63637', 'is')
Annotation(MEKi, 'http://identifiers.org/chebi/90851', 'is')
Annotation(EGF, 'http://identifiers.org/uniprot/P01133', 'is')
Annotation(EGFR, 'http://identifiers.org/uniprot/P00533', 'is')
Annotation(GRB2, 'http://identifiers.org/uniprot/P62993', 'is')
Rule('MAPK1_Y187_base', MAPK1(Y187='p') >> MAPK1(Y187='u'), MAPK1_dephosphorylation_Y187_base_rate)
Rule('MAPK3_Y204_base', MAPK3(Y204='p') >> MAPK3(Y204='u'), MAPK3_dephosphorylation_Y204_base_rate)
Rule('MAPK3_T202_base', MAPK3(T202='p') >> MAPK3(T202='u'), MAPK3_dephosphorylation_T202_base_rate)
Rule('RAF1_phosphorylation_S338_KRAS__N_gtp', RAF1(S338='u') >> RAF1(S338='p'), RAF1_phosphorylation_S338_KRAS__N_gtp_rate)
Rule('RAF1_phosphorylation_S338_HRAS__N_gtp', RAF1(S338='u') >> RAF1(S338='p'), RAF1_phosphorylation_S338_HRAS__N_gtp_rate)
Rule('RAF1_phosphorylation_S338_NRAS__N_gtp', RAF1(S338='u') >> RAF1(S338='p'), RAF1_phosphorylation_S338_NRAS__N_gtp_rate)
Rule('BRAF_phosphorylation_S447_KRAS__N_gtp', BRAF(S447='u') >> BRAF(S447='p'), BRAF_phosphorylation_S447_KRAS__N_gtp_rate)
Rule('BRAF_phosphorylation_S447_HRAS__N_gtp', BRAF(S447='u') >> BRAF(S447='p'), BRAF_phosphorylation_S447_HRAS__N_gtp_rate)
Rule('BRAF_phosphorylation_S447_NRAS__N_gtp', BRAF(S447='u') >> BRAF(S447='p'), BRAF_phosphorylation_S447_NRAS__N_gtp_rate)
Rule('MAP2K1_phosphorylation_S222_RAF1__S338_p', MAP2K1(S222='u', S218='u') >> MAP2K1(S222='p', S218='p'), MAP2K1_phosphorylation_S222_RAF1__S338_p_rate)
Rule('MAP2K1_phosphorylation_S222_BRAF__S447_p', MAP2K1(S222='u', S218='u') >> MAP2K1(S222='p', S218='p'), MAP2K1_phosphorylation_S222_BRAF__S447_p_rate)
Rule('MAP2K2_phosphorylation_S226_RAF1__S338_p', MAP2K2(S222='u', S226='u') >> MAP2K2(S222='p', S226='p'), MAP2K2_phosphorylation_S226_RAF1__S338_p_rate)
Rule('MAP2K2_phosphorylation_S226_BRAF__S447_p', MAP2K2(S222='u', S226='u') >> MAP2K2(S222='p', S226='p'), MAP2K2_phosphorylation_S226_BRAF__S447_p_rate)
Rule('MAPK1_phosphorylation_Y187_MAP2K1__S218_p__S222_p', MAPK1(T185='u', Y187='u') >> MAPK1(T185='p', Y187='p'), MAPK1_phosphorylation_Y187_MAP2K1__S218_p__S222_p_rate)
Rule('MAPK1_phosphorylation_Y187_MAP2K2__S222_p__S226_p', MAPK1(T185='u', Y187='u') >> MAPK1(T185='p', Y187='p'), MAPK1_phosphorylation_Y187_MAP2K2__S222_p__S226_p_rate)
Rule('MAPK3_phosphorylation_Y204_MAP2K1__S218_p__S222_p', MAPK3(Y204='u', T202='u') >> MAPK3(Y204='p', T202='p'), MAPK3_phosphorylation_Y204_MAP2K1__S218_p__S222_p_rate)
Rule('MAPK3_phosphorylation_Y204_MAP2K2__S222_p__S226_p', MAPK3(Y204='u', T202='u') >> MAPK3(Y204='p', T202='p'), MAPK3_phosphorylation_Y204_MAP2K2__S222_p__S226_p_rate)
Initial(FL(inh=None), FL_eq)
Initial(FLT3(Y843='u', inh=None), FLT3_eq)
Initial(HRAS(N='gdp', inh=None), HRAS_eq)
Initial(KRAS(N='gdp', inh=None), KRAS_eq)
Initial(NRAS(N='gdp', inh=None), NRAS_eq)
Initial(RAF1(S338='u', inh=None), RAF1_eq)
Initial(BRAF(S447='u', inh=None), BRAF_eq)
Initial(MAP2K1(S222='u', S218='u', inh=None), MAP2K1_eq)
Initial(MAP2K2(S222='u', S226='u', inh=None), MAP2K2_eq)
Initial(MAPK1(T185='u', Y187='u', inh=None), MAPK1_eq)
Initial(MAPK3(Y204='u', T202='u', inh=None), MAPK3_eq)
Observable('Atot', A())
Observable('Btot', B())
Observable('Ctot', C())
Observable('AB0', A(b=MultiState(None, None, None)), match='species')
Observable('AB1', A(b=MultiState(1, None, None)) % B(a=1), match='species')
Observable('AB2',
A(b=MultiState(1, 2, None)) % B(a=1) % B(a=2),
match='species')
Observable('AB3',
A(b=MultiState(1, 2, 3)) % B(a=1) % B(a=2) % B(a=3),
match='species')
Observable('AB_motif', A(b=1) % B(a=1))
Tag('x')
Expression('f_synth', k_synthC * AB_motif(x)**2)
# A synthesizes C with rate dependent on bound B
Rule('_R1', A() @ x >> A() @ x + C(), f_synth)
# A binds B
Rule('_R2', A(b=None) + B(a=None) | A(b=1) % B(a=1), kp, km)
# degradation of C
Rule('_R3', C() >> None, k_degrC)
Initial(A(b=MultiState(None, None, None)), Ab_b_b_0)
Initial(B(a=None), Ba_0)
Initial(C(), C_0)
# exported from PySB model 'model'
from pysb import Model, Monomer, Parameter, Expression, Compartment, Rule, Observable, Initial, MatchOnce, Annotation, ANY, WILD
Model()
Monomer('A', ['B'])
Monomer('B', ['A'])
Parameter('inhibition_0_A_inhibitor_B_inh_target_2kf_0', 1.5e-05)
Parameter('inhibition_0_A_inhibitor_B_inh_target_1kr_0', 0.00012)
Parameter('A_0', 200000.0)
Parameter('B_0', 50000.0)
Observable('A_obs', A())
Observable('B_obs', B())
Rule('inhibition_0_A_inhibitor_B_inh_target',
A(B=None) + B(A=None) | A(B=1) % B(A=1),
inhibition_0_A_inhibitor_B_inh_target_2kf_0,
inhibition_0_A_inhibitor_B_inh_target_1kr_0)
Initial(A(B=None), A_0)
Initial(B(A=None), B_0)
Observable('AB_complex', A(B=1) % B(A=1))
#Define individual species in model
Monomer('COX2', ['allo', 'cat']) #Cyclooxygenase-2 enzyme
Monomer('AG', ['b']) #2-arachidonoylglycerol, a substrate of COX2
Monomer('AA', ['b']) #arachidonic acid, a substrate of COX2
Monomer('PG') #Prostaglandin, product of COX2 turnover of AA
Monomer('PGG') #Prostaglandin glycerol, product of COX2 turnover of 2-AG
#Initial starting concentrations in micromolar
Parameter('COX2_0', 15e-3)
Parameter('AG_0', 16)
Parameter('AA_0', 16)
Parameter('PG_0', 0)
Parameter('PGG_0', 0)
Initial(COX2(allo=None, cat=None), COX2_0)
Initial(AG(b=None), AG_0)
Initial(AA(b=None), AA_0)
Initial(PG(), PG_0)
Initial(PGG(), PGG_0)
#All kf parameters are in units of inverse microM*s
#All kr parameters are in units of inverse s
#All kcat parameters are in units of inverse s
#the forward reaction is association; the reverse is disassociation
#Rates for AA and COX2 interactions at catalytic site
#AA binding/turnover at catalytic site with nothing in allosteric site
Parameter('kf_AA_cat1', 1000.0)
Parameter('kr_AA_cat1', 830)
Parameter('kcat_AA1', 1.3)
'''
Dimerization model:
A + A <> AA
'''
from pysb import Model, Parameter, Monomer, Rule, Observable, Initial
Model()
#######
V = 100.
#######
Parameter('kf', 0.001)
Parameter('kr', 1.)
Monomer('A', ['d'])
# Rules
Rule('ReversibleBinding', A(d=None) + A(d=None) | A(d=1) % A(d=1), kf, kr)
#Observables
Observable("A_free", A(d=None))
Observable("A_dimer", A(d=1) % A(d=1))
# Inital Conditions
Parameter("A_0", 20.*V)
Initial(A(d=None), A_0)
