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