class Albeck11bPoreTransport(Albeck11b):
k_pore = Parameter(10)
class Smac(Albeck11b.Smac):
M = Species(1e6, override=True)
class CytoC(Albeck11b.CytoC):
M = Species(1e6, override=True)
def add_reactions(self):
yield MichaelisMenten(
self.Bax.A,
self.Smac.M,
self.Bax.A & self.Smac.M,
self.Smac.C,
self.KF,
self.KR,
self.k_pore,
)
yield MichaelisMenten(
self.Bax.A,
self.CytoC.M,
self.Bax.A & self.CytoC.M,
self.CytoC.C,
self.KF,
self.KR,
self.k_pore,
)
class Albeck11dPoreTransport(Albeck11d):
k_pore = Parameter(10)
class Smac(Albeck11d.Smac):
M = Species(1e6, override=True)
KF = Parameter(2 * 1e-6 / 0.07)
class CytoC(Albeck11d.CytoC):
M = Species(1e6, override=True)
def add_reactions(self):
yield MichaelisMenten(
self.Bax.M4,
self.Smac.M,
self.Bax.M4 & self.Smac.M,
self.Smac.C,
self.Smac.KF,
self.KR,
self.k_pore,
)
yield MichaelisMenten(
self.Bax.M4,
self.CytoC.M,
self.Bax.M4 & self.CytoC.M,
self.CytoC.C,
self.KF,
self.KR,
self.k_pore,
)
class Smac(Compartment):
C = Species(0)
M = Species(0)
A = Species(0)
transloc_rates = Parameter(1e-2)
def add_reactions(self):
yield Equilibration(self.C, self.A, self.transloc_rates,
self.transloc_rates)
class Bax(Base.Bax):
M2 = Species(0)
M4 = Species(0)
# Normalized by fractional volume of the mitochondrial membrane compartment
KF = Parameter(1e-6 / 0.07)
KR = Parameter(1e-3)
transloc_rates = Parameter(1e-2)
def add_reactions(self):
# Active Bax translocates to the mitochondria
yield Equilibration(
self.A,
self.M,
self.transloc_rates,
self.transloc_rates,
)
# Bax dimerizes/tetramerizes
yield Equilibration(2 * self.M, self.M2, self.KF, self.KR)
yield Equilibration(2 * self.M2, self.M4, self.KF, self.KR)
class Sensor(Compartment):
sCas3 = Species(0)
sCas9 = Species(0)
sCas8 = Species(0)
sCas3_dimer = Species(7.5e5)
sCas9_dimer = Species(7.5e5)
sCas8_dimer = Species(7.5e5)
kf_sCas3 = Parameter(2 * 2.8e-7)
kr_sCas3 = Parameter(1e-2)
kc_sCas3 = Parameter(1)
kf_sCas9 = Parameter(2 * 2.8e-7)
kf_sCas92 = Parameter(2 * 2e-10)
kr_sCas9 = Parameter(1e-3)
kc_sCas9 = Parameter(1)
kf_sCas8 = Parameter(2 * 5.4e-8)
kr_sCas8 = Parameter(1e-3)
kc_sCas8 = Parameter(1)
class Sensor(Compartment):
sCas3 = Species(0)
sCas9 = Species(0)
sCas8 = Species(0)
sCas3_dimer = Species(1e7)
sCas9_dimer = Species(1e7)
sCas8_dimer = Species(1e7)
kf_sCas3 = Parameter(1e-6)
kr_sCas3 = Parameter(1e-2)
kc_sCas3 = Parameter(1)
kf_sCas9 = Parameter(5e-9)
kr_sCas9 = Parameter(1e-3)
kc_sCas9 = Parameter(1)
kf_sCas8 = Parameter(1e-7)
kr_sCas8 = Parameter(1e-3)
kc_sCas8 = Parameter(1)
class Albeck11d(Base):
k_Bax_C_Bid_T = Parameter(1e-7)
class Bid(Base.Bid):
U = Species(4e4, override=True)
class Bax(Base.Bax):
M2 = Species(0)
M4 = Species(0)
# Normalized by fractional volume of the mitochondrial membrane compartment
KF = Parameter(1e-6 / 0.07)
KR = Parameter(1e-3)
transloc_rates = Parameter(1e-2)
def add_reactions(self):
# Active Bax translocates to the mitochondria
yield Equilibration(
self.A,
self.M,
self.transloc_rates,
self.transloc_rates,
)
# Bax dimerizes/tetramerizes
yield Equilibration(2 * self.M, self.M2, self.KF, self.KR)
yield Equilibration(2 * self.M2, self.M4, self.KF, self.KR)
def add_reactions(self):
yield MichaelisMenten(
self.Bid.T,
self.Bax.C,
self.Bid.T & self.Bax.C,
self.Bax.A,
self.k_Bax_C_Bid_T,
self.KR,
self.KC,
)
# Bcl2 inhibits Bax, Bax2, and Bax4
for x in (self.Bax.M, self.Bax.M2, self.Bax.M4):
yield ReversibleSynthesis(
x,
self.Bcl2,
x & self.Bcl2,
self.Bax.KF,
self.KR,
)
class AlbeckAsMatlab(Albeck11ePoreTransport):
Bcl2c = Species(2e4)
k_Bid_U_C8_A = Parameter(1e-7)
def add_reactions(self):
yield ReversibleSynthesis(
self.Bid.T, self.Bcl2c, self.Bid.T & self.Bcl2c, self.KF, self.KR
)
def override_reactions(self):
yield MichaelisMenten(
self.C8.A,
self.Bid.U,
self.C8.A & self.Bid.U,
self.Bid.T,
self.k_Bid_U_C8_A,
self.KR,
self.KC,
)
class Albeck11b(Base):
k_Bax_C_Bid_T = Parameter(1e-7)
class Bid(Base.Bid):
U = Species(1e5, override=True)
def add_reactions(self):
yield MichaelisMenten(
self.Bid.T,
self.Bax.C,
self.Bid.T & self.Bax.C,
self.Bax.A,
self.k_Bax_C_Bid_T,
self.KR,
self.KC,
)
yield ReversibleSynthesis(
self.Bax.A,
self.Bcl2,
self.Bax.A & self.Bcl2,
self.KF,
self.KR,
)
class Albeck11c(Base):
k_Bax_C_Bid_T = Parameter(1e-7)
class Bid(Base.Bid):
U = Species(4e4, override=True)
class Bax(Base.Bax):
A2 = Species(0)
A4 = Species(0)
KF = Parameter(1e-6)
KR = Parameter(1e-3)
def add_reactions(self):
# Bax dimerizes/tetramerizes
yield Equilibration(2 * self.A, self.A2, self.KF, self.KR)
yield Equilibration(2 * self.A2, self.A4, self.KF, self.KR)
def add_reactions(self):
yield MichaelisMenten(
self.Bid.T,
self.Bax.C,
self.Bid.T & self.Bax.C,
self.Bax.A,
self.k_Bax_C_Bid_T,
self.KR,
self.KC,
)
# Bcl2 inhibits Bax, Bax2, and Bax4
for x in (self.Bax.A, self.Bax.A2, self.Bax.A4):
yield ReversibleSynthesis(
x,
self.Bcl2,
x & self.Bcl2,
self.KF,
self.KR,
)
class CytoC(Albeck11f.CytoC):
M = Species(1e6, override=True)
KF = Parameter(2 * 1e-6 / 0.07)
class Smac(Albeck11f.Smac):
M = Species(1e6, override=True)
KF = Parameter(2 * 1e-6 / 0.07)
class Base(Compartment):
KF = Parameter(1e-6)
KR = Parameter(1e-3)
KC = Parameter(1)
L = Species(3000)
R = Species(200)
DISC = Species(0)
flip = Species(100)
class C8(Compartment):
pro = Species(2e4)
A = Species(0)
BAR = Species(1e3)
class Bid(Compartment):
U = Species(0)
T = Species(0)
M = Species(0)
class Bax(Compartment):
C = Species(1e5)
M = Species(0)
A = Species(0)
Bcl2 = Species(2e4)
class CytoC(Compartment):
C = Species(0)
M = Species(0)
A = Species(0)
transloc_rates = Parameter(1e-2)
def add_reactions(self):
yield Equilibration(self.C, self.A, self.transloc_rates,
self.transloc_rates)
class Smac(Compartment):
C = Species(0)
M = Species(0)
A = Species(0)
transloc_rates = Parameter(1e-2)
def add_reactions(self):
yield Equilibration(self.C, self.A, self.transloc_rates,
self.transloc_rates)
class Apaf(Compartment):
I = Species(1e5) # noqa: #741
A = Species(0)
Apop = Species(0)
class C3(Compartment):
pro = Species(1e4)
A = Species(0)
ub = Species(0)
class C6(Compartment):
pro = Species(1e4)
A = Species(0)
C9 = Species(1e5)
class PARP(Compartment):
U = Species(1e6)
C = Species(0)
XIAP = Species(1e5)
k_L_R = Parameter(4e-7)
k_DISC = Parameter(1e-5)
k_Apaf_I_Cyto_C = Parameter(5e-7)
k_Apop = Parameter(5e-8)
k_Apop_C3_pro = Parameter(5e-9)
k_Apop_XIAP = Parameter(2e-6)
k_Smac_A_XIAP = Parameter(7e-6)
k_C3_pro_C8_A = Parameter(1e-7)
k_C3_A_XIAP = Parameter(2e-6)
k_C3_ub = Parameter(1e-1)
k_PARP_C = Parameter(1e-2)
k_C6_A_C8_pro = Parameter(3e-8)
# rec_to_bid
# =====================
# tBID Activation Rules
# ---------------------
# L + R <--> L:R --> DISC
# pC8 + DISC <--> DISC:pC8 --> C8 + DISC
# Bid + C8 <--> Bid:C8 --> tBid + C8
def add_reactions(self):
yield CatalyzeConvert(
self.L,
self.R,
self.L & self.R,
self.DISC,
self.k_L_R,
self.KR,
self.k_DISC,
)
yield MichaelisMenten(
self.DISC,
self.C8.pro,
self.DISC & self.C8.pro,
self.C8.A,
self.KF,
self.KR,
self.KC,
)
yield MichaelisMenten(
self.C8.A,
self.Bid.U,
self.C8.A & self.Bid.U,
self.Bid.T,
self.KF,
self.KR,
self.KC,
)
# ---------------------
# Inhibition Rules
# ---------------------
# flip + DISC <--> flip:DISC
# C8 + BAR <--> BAR:C8
# ---------------------
yield ReversibleSynthesis(self.DISC, self.flip, self.DISC & self.flip,
self.KF, self.KR)
yield ReversibleSynthesis(self.BAR, self.C8.A, self.BAR & self.C8.A,
self.KF, self.KR)
# Apoptosome formation
# --------------------
# Apaf + cCytoC <--> Apaf:cCytoC --> aApaf + cCytoC
# aApaf + pC9 <--> Apop
# Apop + pC3 <--> Apop:pC3 --> Apop + C3
yield MichaelisMenten(
self.CytoC.A,
self.Apaf.I,
self.CytoC.A & self.Apaf.I,
self.Apaf.A,
self.k_Apaf_I_Cyto_C,
self.KR,
self.KC,
)
yield ReversibleSynthesis(self.Apaf.A, self.C9, self.Apop, self.k_Apop,
self.KR)
yield MichaelisMenten(
self.Apop,
self.C3.pro,
self.Apop & self.C3.pro,
self.C3.A,
self.k_Apop_C3_pro,
self.KR,
self.KC,
)
# Apoptosome-related inhibitors
# -----------------------------
# Apop + XIAP <--> Apop:XIAP
# cSmac + XIAP <--> cSmac:XIAP
yield ReversibleSynthesis(self.Apop, self.XIAP, self.Apop & self.XIAP,
self.k_Apop_XIAP, self.KR)
yield ReversibleSynthesis(self.Smac.A, self.XIAP,
self.Smac.A & self.XIAP, self.k_Smac_A_XIAP,
self.KR)
# Caspase reactions
# -----------------
# Includes effectors, inhibitors, and feedback initiators:
#
# pC3 + C8 <--> pC3:C8 --> C3 + C8 CSPS
# pC6 + C3 <--> pC6:C3 --> C6 + C3 CSPS
# XIAP + C3 <--> XIAP:C3 --> XIAP + C3_U CSPS
# PARP + C3 <--> PARP:C3 --> CPARP + C3 CSPS
# pC8 + C6 <--> pC8:C6 --> C8 + C6 CSPS
yield MichaelisMenten(
self.C8.A,
self.C3.pro,
self.C8.A & self.C3.pro,
self.C3.A,
self.k_C3_pro_C8_A,
self.KR,
self.KC,
)
yield MichaelisMenten(
self.XIAP,
self.C3.A,
self.XIAP & self.C3.A,
self.C3.ub,
self.k_C3_A_XIAP,
self.KR,
self.k_C3_ub,
)
yield MichaelisMenten(
self.C3.A,
self.PARP.U,
self.C3.A & self.PARP.U,
self.PARP.C,
self.KF,
self.k_PARP_C,
self.KC,
)
yield MichaelisMenten(
self.C3.A,
self.C6.pro,
self.C3.A & self.C6.pro,
self.C6.A,
self.KF,
self.KR,
self.KC,
)
yield MichaelisMenten(
self.C6.A,
self.C8.pro,
self.C6.A & self.C8.pro,
self.C8.A,
self.k_C6_A_C8_pro,
self.KR,
self.KC,
)
class ARM(AlbeckAsMatlab):
L = Species(0, override=True) # Set extrinsic stimuli to 0
IntrinsicStimuli = Species(0) # Add intrinsic stimuli
class Smac(AlbeckAsMatlab.Smac):
M = Species(1e5, override=True)
class CytoC(AlbeckAsMatlab.CytoC):
M = Species(1e5, override=True)
class Apaf(AlbeckAsMatlab.Apaf):
I = Species(1e3, override=True) # noqa: E741
C9 = Species(0, override=True)
XIAP = Species(1e4, override=True)
k_Apaf_A_C3_pro = Parameter(5e-9) # _Pore_to_PARP.k_Apop_C3_pro
k_Apaf_A_C3_A = Parameter(1.3e-6)
k_Apaf_A_XIAP = Parameter(2e-6) # _Pore_to_PARP.k_C3_A_XIAP
class Sensor(Compartment):
sCas3 = Species(0)
sCas9 = Species(0)
sCas8 = Species(0)
sCas3_dimer = Species(7.5e5)
sCas9_dimer = Species(7.5e5)
sCas8_dimer = Species(7.5e5)
kf_sCas3 = Parameter(2 * 2.8e-7)
kr_sCas3 = Parameter(1e-2)
kc_sCas3 = Parameter(1)
kf_sCas9 = Parameter(2 * 2.8e-7)
kf_sCas92 = Parameter(2 * 2e-10)
kr_sCas9 = Parameter(1e-3)
kc_sCas9 = Parameter(1)
kf_sCas8 = Parameter(2 * 5.4e-8)
kr_sCas8 = Parameter(1e-3)
kc_sCas8 = Parameter(1)
def add_reactions(self):
# Apoptosome formation
# aApaf + pC3 <--> aApaf:pC3 --> aApaf + C3
# C3 + aApaf <--> C3:aApaf --> C3 + Apop
yield MichaelisMenten(
self.Apaf.A,
self.C3.pro,
self.Apaf.A & self.C3.pro,
self.C3.A,
self.k_Apaf_A_C3_pro,
self.KR,
self.KC,
)
yield MichaelisMenten(
self.C3.A,
self.Apaf.A,
self.Apaf.A & self.C3.A,
self.Apop,
self.k_Apaf_A_C3_A,
self.KR,
self.KC,
)
# Apoptosome-related inhibitors
# Apaf + XIAP <--> Apaf:XIAP
yield ReversibleSynthesis(
self.Apaf.A, self.XIAP, self.Apaf.A & self.XIAP, self.k_Apaf_A_XIAP, self.KR
)
# Sensors
yield MichaelisMenten(
self.C3.A,
self.Sensor.sCas3_dimer,
self.C3.A & self.Sensor.sCas3_dimer,
2 * self.Sensor.sCas3,
self.Sensor.kf_sCas3,
self.Sensor.kr_sCas3,
self.Sensor.kc_sCas3,
)
yield MichaelisMenten(
self.Apop,
self.Sensor.sCas9_dimer,
self.Apop & self.Sensor.sCas9_dimer,
2 * self.Sensor.sCas9,
self.Sensor.kf_sCas9,
self.Sensor.kr_sCas9,
self.Sensor.kc_sCas9,
)
yield MichaelisMenten(
self.C8.A,
self.Sensor.sCas8_dimer,
self.C8.A & self.Sensor.sCas8_dimer,
2 * self.Sensor.sCas8,
self.Sensor.kf_sCas8,
self.Sensor.kr_sCas8,
self.Sensor.kc_sCas8,
)
# Add interaction between single activation
yield MichaelisMenten(
self.Apaf.A,
self.Sensor.sCas9_dimer,
self.Apaf.A & self.Sensor.sCas9_dimer,
2 * self.Sensor.sCas9,
self.Sensor.kf_sCas92,
self.Sensor.kr_sCas9,
self.Sensor.kc_sCas9,
)
yield MichaelisMenten(
self.IntrinsicStimuli,
self.Bid.U,
self.IntrinsicStimuli & self.Bid.U,
self.Bid.T,
self.KF,
self.KR,
self.KC,
)
@classmethod
def _reactions_to_remove(self):
# aApaf + pC9 <--> Apop
yield ReversibleSynthesis(self.Apaf.A, self.C9, self.Apop, self.k_Apop, self.KR)
# Apop + XIAP <--> Apop:XIAP
yield ReversibleSynthesis(
self.Apop, self.XIAP, self.Apop & self.XIAP, self.k_Apop_XIAP, self.KR
)