RuleHub/Examples/biology/dnadamagerepair/dna-damage-repair.bngl at 4063fbdec91c54baa4fe7914ae48ba56815eb6e3 · akutuva21/RuleHub · GitHub

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begin model
begin parameters
    # DNA damage sensing and repair pathway (ATM-CHK2-p53 axis)

    # Damage induction
    k_damage 0.1       # DNA lesion formation (e.g. UV,ROS)

    # Sensing & Signaling
    k_sense 1.5        # MRN complex sensing lesions
    k_atm_act 10.0      # ATM activation by MRN/DNA complexes
    k_chk2_phos 10.0    # Chk2 phosphorylation by active ATM

    # Effector activation
    k_repair_rec 100.0   # Recruitment of PARP/Ligase complexes
    k_repair_act 10.0   # Actual repair execution

    # Recovery
    k_reset 0.05       # Phosphatase relay
    k_turnover 0.02    # Basal protein degradation

    # Initials
    DNA_intact 100
    MRN_tot 50          # Sensor complex
    ATM_tot 100         # Master kinase
    Chk2_tot 150        # Transducer kinase
    Repair_tot 80       # Effector machinery
end parameters

begin molecule types
    DNA(state~intact~damaged~repaired)
    MRN(b,r,state~U~A)
    ATM(b,state~U~A)
    Chk2(b,state~U~P)
    RepairComplex(b,state~avail~engaged)
end molecule types

begin seed species
    DNA(state~intact) DNA_intact
    MRN(b,r,state~U) MRN_tot
    ATM(b,state~U) ATM_tot
    Chk2(b,state~U) Chk2_tot
    RepairComplex(b,state~avail) Repair_tot
end seed species

begin observables
    # KEY BIOLOGICAL OUTPUTS
    Molecules Lesion_Load     DNA(state~damaged)         # Unrepaired damage count
    Molecules Active_Sensor   MRN(state~A)               # Detection signal
    Molecules Kinase_Relay   ATM(state~A),Chk2(state~P) # Signaling intensity
    Molecules Repair_In_Work RepairComplex(state~engaged) # Effector engagement
    Molecules Final_Integrity DNA(state~repaired)        # Success metric
end observables

begin reaction rules
    ## SENSING PHASE
    # DNA damage occurs
    DNA(state~intact) -> DNA(state~damaged) k_damage

    # MRN complex senses damage and becomes active
    DNA(state~damaged) + MRN(b,state~U) <-> DNA(state~damaged!1).MRN(b!1,state~U) 1.0,0.1
    DNA(state~damaged!1).MRN(b!1,state~U) -> DNA(state~damaged!1).MRN(b!1,state~A) k_sense  # Conformational activation

    ## SIGNALING PHASE
    # Active MRN recruits and activates ATM
    MRN(state~A,r) + ATM(state~U,b) <-> MRN(state~A,r!2).ATM(state~U,b!2) k_atm_act,0.1
    MRN(state~A,r!2).ATM(state~U,b!2) -> MRN(state~A,r!2).ATM(state~A,b!2) 1.0

    # ATM phosphorylates Chk2
    ATM(state~A) + Chk2(state~U) -> ATM(state~A) + Chk2(state~P) k_chk2_phos

    ## REPAIR PHASE
    # Activated signaling recruits repair machinery
    Chk2(state~P) + RepairComplex(state~avail,b) <-> Chk2(state~P!1).RepairComplex(state~avail,b!1) k_repair_rec,0.1
    Chk2(state~P!1).RepairComplex(state~avail,b!1) -> Chk2(state~P!1).RepairComplex(state~engaged,b!1) 1.0

    # Engaged repair machinery fixes DNA
    RepairComplex(state~engaged) + DNA(state~damaged) -> RepairComplex(state~engaged) + DNA(state~repaired) k_repair_act

    ## CLEARANCE
    ATM(state~A) -> ATM(state~U) k_reset
    Chk2(state~P) -> Chk2(state~U) k_reset
    RepairComplex(state~engaged) -> RepairComplex(state~avail) k_reset
    MRN(state~A) -> MRN(state~U) k_reset
end reaction rules

begin actions
    generate_network({overwrite=>1})
    simulate({method=>"ode",t_end=>100,n_steps=>300})
end actions
end model