def cui_direct1(do_pore_transport=False):
"""The "direct 1" model drawn from [Cui2008]_.
Builds on the (base) direct model from [Cui2008]_,
implemented in :py:func:`cui_direct` (see source code).
Parameters
----------
do_pore_transport : True or False (default)
As for :py:func:`chen_biophys_j`.
"""
alias_model_components()
# Build on the base "direct" model...
cui_direct(do_pore_transport=do_pore_transport)
# ...by adding inhibition of Bax by Bcl2,
bind(Bax(state='A', s1=None, s2=None), Bcl2, [5e6/(N_A*V), 0.001])
# ...associated displacement reactions
displace_reversibly(Bax(active_monomer), Bid(state='T'), Bcl2,
[5e6/(N_A*V), 0.001])
displace_reversibly(Bad(state='M'), Bax(active_monomer), Bcl2,
[1e5/(N_A*V), 0.005])
# ...and degradation of the active Bax:Bcl2 complex
degrade(Bax(bf=1) % Bcl2(bf=1), 0.005)
def cui_direct1(do_pore_transport=False):
"""The "direct 1" model drawn from [Cui2008]_.
Builds on the (base) direct model from [Cui2008]_,
implemented in :py:func:`cui_direct` (see source code).
Parameters
----------
do_pore_transport : True or False (default)
As for :py:func:`chen_biophys_j`.
"""
alias_model_components()
# Build on the base "direct" model...
cui_direct(do_pore_transport=do_pore_transport)
# ...by adding inhibition of Bax by Bcl2,
bind(Bax(state='A', s1=None, s2=None), Bcl2, [5e6 / (N_A * V), 0.001])
# ...associated displacement reactions
displace_reversibly(Bax(active_monomer), Bid(state='T'), Bcl2,
[5e6 / (N_A * V), 0.001])
displace_reversibly(Bad(state='M'), Bax(active_monomer), Bcl2,
[1e5 / (N_A * V), 0.005])
# ...and degradation of the active Bax:Bcl2 complex
degrade(Bax(bf=1) % Bcl2(bf=1), 0.005)
Monomer('NFkB_nn', ['s'])
Monomer('A20', ['s'])
Monomer('A20t', ['s'])
Monomer('IkBa', ['s', 'k'], {'s': ['u', 'p']})
Monomer('IkBan', ['s'])
Monomer('IkBat', ['s'])
Monomer('IkBa|NFkBc', ['n', 'c'])
Monomer('IkBan|NFkB_nn', ['s'])
Monomer('IKKi',['s'], {'s': ['u', 'p']})
#TNFa binds to TNFR1 to activate receptor then inactivates and degrades
Parameter('kb', 1.2*10^-5)
Parameter('kf', 1.2*10^-3)
Parameter('TNFa_deg', 2*10^-4)
Rule('TNFa_bind_TNFR1', TNFa(b=None) % TNFR1(b=None), (kb,kf))
degrade('TNFa', TNFa_deg)
#IKKK in active state (IKKKa) (ODE 1)
Parameter('ka',2e-05)
Parameter('Kn', 10^5)
Parameter('Ka20', 10^5)
Parameter('ki', .01)
Parameter('B', 0)
Parameter('A20', 10000)
Parameter('RIF')
Parameter('IKKKa', 0)
Rule('RIP|TRAF2', RIF(b=None), TRAF2(b=None), kf)
Rule('IKKK_bind_B', IKKK(b=None) + B(b=None) >> IKKK(b=1)%B(b=1), Ka)
degrade("IKKK", ki)
#Expression('aIKKK', ka*B*(kn-IKKKa)*ka20/(ka20+A20)-ki*IKKKa)
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
equilibrate(Cdh1(b=None,S='i'),Cdh1(b=None, S='a'),[kfCdh1, krCdh1])
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",
p27_p21(b=None, S="u") + Cb(b=1, S="a") % Cdk1(b=1, c=None, S="a")
Parameter('kf7', 1.0e-06)
Parameter('kr7', 1.0e-03)
Parameter('kc7', 1.0e-00)
catalyze_state(MOMP_sig(state='active'), 'b', EC(), 'b', 'state', 'inactive',
'active', [kf7, kr7, kc7])
# 10. PARP Cleavage: *eCaspases-> PARP --> cPARP kf8, kr8, kc8
Parameter('kf8', 1.0e-06)
Parameter('kr8', 1.0e-03)
Parameter('kc8', 1.0e-00)
catalyze_state(EC(state='active'), 'b', PARP(), 'b', 'state', 'unmod',
'cleaved', [kf8, kr8, kc8])
# 11. Initiator Caspase Degradation *eCaspase --> None
Parameter('kc9', 1.0e-06)
degrade(IC(state='active'), kc9)
# 12. Unrelated Signaling
Parameter('kf10', 1.0e-05)
Parameter('kr10', 1.0e-03)
Parameter('kc10', 5.0e-04)
catalyze_state(USM1(state='active'), 'b', USM2(), 'b', 'state', 'inactive',
'active', [kf10, kr10, kc10])
catalyze_state(USM2(state='active'), 'b', USM3(), 'b', 'state', 'inactive',
'active', [kf10, kr10, kc10])
catalyze_state(USM3(state='active'), 'b', USM1(), 'b', 'state', 'inactive',
'active', [kf10, kr10, kc10])
# 13. Unrelated Signaling
Parameter('kf11', 1.0e-05)
Parameter('kr11', 1.0e-03)
[cdk4_6(S = 'i'), None, cdk4_6_rates]])
equilibrate(pRB(b=None,S='u'),pRB(b=None,S='p'),[kfprb,krprb]
equilibrate(pRB(b=None,S='p'),pRB(b=None,S='pp'),[kfprbp,krprbp]
equilibrate(E2F(b=None,S='u'),E2F(b=None, S='p'),[kfEp, krEp]
catalyze(Ce(b=1)%Cdk2(b=1,S='a'), 'b', pRB(S='p'), 'b', pRB(S='pp'), (kfCe, krCe, kcaCe))
catalyze(Ca(b=1)%Cdk2(b=1,S='a'), 'b', E2F(S='u'), 'b', E2F(S='p'), (kfCa, krCa, kcaCa))
catalyze(Cd(b=1)%Cdk4_6(b=1,S='a'), 'b', pRB(S='u'), 'b', pRB(S='p'), (kfCd, krCd, kcaCd))
catalyze(Cd(b=1) % Cdk4_6(b=1,b=2 S ='a') % p27_p21(b=2)), 'b', pRB(S='u'), 'b', pRB(S='p'), (kfCdp, krCdp, kcaCdp))
#Rule for degradation of AP1
degrade(AP1(), kdap1)
#Degradation of CyclinD
degrade(Cd(),kdCd)
#Rules replaced above by Bind:
#pRB inhibits Cyclin D
#Rule('pRB_Cd__bind', pRB(b=None, S= 'u') + Cd(b=None, S = 'i') <> pRB(b=1, S='u') % Cd(b=1, S= 'i'), *[kfi7, kri7]) #this can use bind
#pRBp inhibits Cyclin D
#Rule('pRBp_Cd__bind', pRB(b=None, S= 'p') + Cd(b=None, S = 'i') <> pRB(b=1, S='p') % Cd(b=1, S= 'i'), *[kfi8, kri8]) #this can use bind
#Rule('Cd_Cdk4_6_bind', Cd(b=None, S='a') + Cdk4_6(b=None, S='i') <> Cd(b=1) % Cdk4_6(b=1, S= 'i'), *[kcom1, kdecom1]) #this can use bind
