Example #1
0
    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)
Example #2
0
    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)
Example #3
0
    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)
Example #4
0
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,
        )
Example #5
0
    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)
Example #6
0
    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)
Example #7
0
 class Smac(Albeck11b.Smac):
     M = Species(1e6, override=True)
Example #8
0
 class Smac(AlbeckAsMatlab.Smac):
     M = Species(1e5, override=True)
Example #9
0
 class C6(Compartment):
     pro = Species(1e4)
     A = Species(0)
Example #10
0
 class Apaf(Compartment):
     I = Species(1e5)  # noqa: #741
     A = Species(0)
Example #11
0
 class Smac(Albeck11f.Smac):
     M = Species(1e6, override=True)
     KF = Parameter(2 * 1e-6 / 0.07)
Example #12
0
 class Mito(Compartment):
     I = Species(5e5)  # noqa: #741
     A = Species(0)
Example #13
0
 class Bax(Compartment):
     C = Species(1e5)
     M = Species(0)
     A = Species(0)
Example #14
0
class Corbat2018(AlbeckAsMatlab):
    L = Species(0, override=True)  # Set extrinsic stimuli to 0
    IntrinsicStimuli = Species(0)  # Add intrinsic stimuli

    XIAP = Species(1e2, override=True)
    R = Species(1e3, override=True)

    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)

    def add_reactions(self):
        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,
        )
        yield MichaelisMenten(
            self.IntrinsicStimuli,
            self.Bid.U,
            self.IntrinsicStimuli & self.Bid.U,
            self.Bid.T,
            self.KF,
            self.KR,
            self.KC,
        )
Example #15
0
class ARM_intrinsic(ARM):
    IntrinsicStimuli = Species(1e2, override=True)
Example #16
0
class ARM_extrinsic(ARM):
    L = Species(1e3, override=True)
Example #17
0
 class Apaf(AlbeckAsMatlab.Apaf):
     I = Species(1e3, override=True)  # noqa: E741
Example #18
0
 class CytoC(AlbeckAsMatlab.CytoC):
     M = Species(1e5, override=True)
Example #19
0
 class Bid(Base.Bid):
     U = Species(4e4, override=True)
Example #20
0
class Corbat2018_extrinsic(Corbat2018):
    L = Species(1e3, override=True)
Example #21
0
 class CytoC(Albeck11d.CytoC):
     M = Species(1e6, override=True)
Example #22
0
class Corbat2018_intrinsic(Corbat2018):
    IntrinsicStimuli = Species(1e2, override=True)
Example #23
0
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,
        )
Example #24
0
 class C8(Compartment):
     pro = Species(2e4)
     A = Species(0)
Example #25
0
 class CytoC(Albeck11f.CytoC):
     M = Species(1e6, override=True)
     KF = Parameter(2 * 1e-6 / 0.07)
Example #26
0
 class Bid(Base.Bid):
     U = Species(1e5, override=True)
Example #27
0
 class C3(Compartment):
     pro = Species(1e4)
     A = Species(0)
     ub = Species(0)
Example #28
0
 class Bid(Compartment):
     U = Species(0)
     T = Species(0)
     M = Species(0)
Example #29
0
 class PARP(Compartment):
     U = Species(1e6)
     C = Species(0)
Example #30
0
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
        )