def setUp(self):
""" Setup for Solver() tests """
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))
synthesize(A(a=None), ksynthA)
synthesize(B(b=None), ksynthB)
Rule('AB_bind', A(a=None) + B(b=None) >> A(a=1) % B(b=1), kbindAB)
time = np.linspace(0, 0.005, 101)
self.solver = Solver(model, time)
self.solver_lsoda = Solver(model, time, integrator='lsoda')
self.solver_lsoda_jac = Solver(model, time, integrator='lsoda',
use_analytic_jacobian=True)
Parameter('i1', .01)
Parameter('c6a', .00002)
degrade(IkBa(), c6a)
#Expression('fNFkB',c6a*IkBa|NFkB_c-a1*NFkBc*IkBa +tp*IkBa|NFkBp)
Rule('trans_NFkB_Nuc', NFkB(b=None) <> NFkB(b=None), i1)
#Free Nuclear nFkB (ODE8)
Parameter('kv', 5)
Parameter('IkBan',.06*10^-5)
Expression('fNFkBn', -a1*kv*IkBan*NFkBn)
#A20 Protein (ODE 9)
Parameter('c4', .5)
Parameter('A20t', 10)
Parameter('c5', .0005)
synthesize(A20t(), c4)
degrade(A20(), c5)
#A20 Transcript (ODE10)
Parameter('c1', .01)
Parameter('G', 0)
Parameter('c3', .00075)
Rule('Synthesize_NFkB')
Rule('degrad_A20t')
#Free Cytoplasmic IkBa protein (ODE11)
Parameter('a2', 10^-7)
Parameter('IkBa', .14*10^-5)
Parameter('IkBat', 10)
Parameter('c5a', .0001)
Parameter('i1a', .002)
Parameter('p27_21_0', 1.0e01) #Y10 in Iwamoto
Initial(p27_p21(b=None, S='u'),p27_21_0)
Parameter('Ca_Cdk2_p27_p21_0', 1.0e-04) #Y13 in Iwamoto
Initial(Ca(b=1, S='a') % Cdk2(b=1, c=2, S='a') % p27_p21(b=2, S='u'), Ca_Cdk2_p27_p21_0)
Parameter('CDC25_0', 1.0e01) #THIS PARAMETER IS NOT CORRECT- ESTIMATED FOR NOW- NOT IN IWAMOTO PAPER
Initial(CDC25(b=None, S='i'), CDC25_0)
#Declare Rules
#E2F promotes the synthesis of Cyclin A
#I can show synthesis, as shown below, but how do I show the promotion part????
#Cyclin A Synthesis and Degradation
synthesize(Ca(b=None, S = 'a'), kSCa)
degrade(Ca(b=None, S='a'),kDCa)
#Cyclin A binds to Cdk2
Rule('Ca_Cdk2_bind',Ca(b=None, S='a') + Cdk2(b=None, c=None, S='i') <> Ca(b=1, S='a') % Cdk2(b=1, c=None, S ='i'), *[kcdk2f, kcdk2r])
#The Ca/Cdk2 complex equilibrates from inactive to active
equilibrate(Ca(b=1, S='a') % Cdk2(b=1, c=None, S='i'),Ca(b=1, S='a') % Cdk2(b=1, c=None, S='a'),[kfcacdk,krcacdk])
#The Ca/Cdk2 complex binds to p27_p21 - this complex is inactive
Rule ('Ca_Cdk2_p27_p21_bind',p27_p21(b=None, S='u') + Ca(b=1, S='a') % Cdk2(b=1, c=None, S='a') <> Ca(b=1, S='i') % Cdk2(b=1, c=2, S ='i') % p27_p21(b=2, S='u') , *[kfcp27_p21, krcp27_p21])
#Equilibrate CDC25
equilibrate(CDC25(b=None,S='i'),CDC25(b=None, S='a'),[kfCDC25, krCDC25])
#Equilibrate Cdh1
Parameter('k1', 0.015*NA_V)
Parameter('k2', 0)
Parameter('k3', 200/NA_V)
Parameter('k4', 2*180/NA_V/NA_V)
Parameter('kp4', 0.018)
Parameter('k5', 0)
Parameter('k6', 1.0)
Parameter('k7', 0.6)
Parameter('k8', 1e6) #1e12)
Parameter('k9', 1e3) #1e6)
Monomer('cyclin', ['Y', 'b'], {'Y': ['U','P']})
Monomer('cdc2', ['Y', 'b'], {'Y': ['U','P']})
# Rule 1
synthesize(cyclin(Y='U', b=None), k1)
# Rule 2
#degrade(cyclin(Y='U', b=None), k2)
# Rule 3
Rule('BindingAndPhosphoylation', cyclin(Y='U', b=None) + cdc2(Y='P', b=None) >> cyclin(Y='P', b=1) % cdc2(Y='P', b=1), k3)
# Rule 4
Rule('Activation', cyclin(Y='P', b=1) % cdc2(Y='P', b=1) >> cyclin(Y='P', b=1) % cdc2(Y='U', b=1), kp4)
# Rule 4'
Rule('Autocatalytic', cyclin(Y='P', b=1) % cdc2(Y='P', b=1) + cyclin(Y='P', b=2) % cdc2(Y='U', b=2) + cyclin(Y='P', b=2) % cdc2(Y='U', b=2) >>
cyclin(Y='P', b=1) % cdc2(Y='U', b=1) + cyclin(Y='P', b=2) % cdc2(Y='U', b=2) + cyclin(Y='P', b=2) % cdc2(Y='U', b=2), k4)
# Rule 5
Initial(Cb(b=1, S="a") % Cdk1(b=1, c=None, S="a"), Cb_Cdk1a_0)
Parameter("p27_21_0", 1.0e01) # Y10 in Iwamoto
Initial(p27_p21(b=None, S="u"), p27_21_0)
Parameter("Cb_Cdk1_p27_p21_0", 1.0e-04) # VALUE NOT CORRECT
Initial(Cb(b=1, S="a") % Cdk1(b=1, c=2, S="a") % p27_p21(b=2, S="u"), Cb_Cdk1_p27_p21_0)
Parameter("CDC25_0", 1.0e01) # THIS PARAMETER IS NOT CORRECT- ESTIMATED FOR NOW- NOT IN IWAMOTO PAPER
Initial(CDC25(b=None, S="i"), CDC25_0)
# Declare Rules
# Cyclin B Synthesis and Degradation
synthesize(Cb(b=None, S="a"), kSCb)
degrade(Cb(b=None, S="a"), kDCb)
# Cyclin B binds to Cdk1
Rule(
"Cb_Cdk1_bind",
Cb(b=None, S="a") + Cdk1(b=None, c=None, S="i") <> Cb(b=1, S="a") % Cdk1(b=1, c=None, S="i"),
*[kcdk1f, kcdk1r]
)
# The Cb/Cdk1 complex equilibrates from inactive to active
equilibrate(Cb(b=1, S="a") % Cdk1(b=1, c=None, S="i"), Cb(b=1, S="a") % Cdk1(b=1, c=None, S="a"), [kfcbcdk, krcbcdk])
# The Cb/Cdk1 complex binds to p27_p21 - this complex is inactive
Rule(
"Cb_Cdk1_p27_p21_bind",
