begin name
passos1
end name

begin reactions
ATMInactivation {1.0}ATMA = {1.0}ATMI
ATMactivation {1.0}damDNA + {1.0}ATMI = {1.0}damDNA + {1.0}ATMA
DNAdamage {1.0}IR = {1.0}IR + {1.0}damDNA
DNArepair {1.0}damDNA = {1.0}$Sink
GADD45activation2 {1.0}p21 = {1.0}p21 + {1.0}GADD45
GADD45degradation {1.0}GADD45 = {1.0}$Sink
Mdm2Degradation {1.0}Mdm2 = {1.0}$Sink
Mdm2Pdegradation {1.0}Mdm2P = {1.0}$Sink
Mdm2Synthesis {1.0}Mdm2mRNA = {1.0}Mdm2mRNA + {1.0}Mdm2
Mdm2dephosorylation {1.0}Mdm2P = {1.0}Mdm2
Mdm2mRNADegradation {1.0}Mdm2mRNA = {1.0}$Sink
Mdm2mRNASynthesis1 {1.0}p53 = {1.0}p53 + {1.0}Mdm2mRNA
Mdm2mRNASynthesis2 {1.0}p53P = {1.0}p53P + {1.0}Mdm2mRNA
Mdm2phoshorylation {1.0}Mdm2 + {1.0}ATMA = {1.0}Mdm2P + {1.0}ATMA
P53Mdm2Binding {1.0}p53 + {1.0}Mdm2 = {1.0}Mdm2p53
P53Mdm2Release {1.0}Mdm2p53 = {1.0}p53 + {1.0}Mdm2
ROSDNAdamage {1.0}ROS = {1.0}ROS + {1.0}damDNA
ROSgenerationP38 {1.0}p38P = {1.0}p38P + {1.0}ROS
ROSremoval {1.0}ROS = {1.0}$Sink
basalROSDNAdamage {1.0}basalROS = {1.0}basalROS + {1.0}damDNA
p21Synthesis1 {1.0}p21mRNA = {1.0}p21mRNA + {1.0}p21step1
p21Synthesis2 {1.0}p21step1 = {1.0}p21step2
p21Synthesis3 {1.0}p21step2 = {1.0}p21
p21degradation {1.0}p21 = {1.0}$Sink
p21mRNADegradation {1.0}p21mRNA = {1.0}$Sink
p21mRNASynthesis1 {1.0}p53 = {1.0}p53 + {1.0}p21mRNA
p21mRNASynthesis2 {1.0}p53P = {1.0}p53P + {1.0}p21mRNA
p38activation {1.0}p38 + {1.0}GADD45 = {1.0}p38P + {1.0}GADD45
p38inactivation {1.0}p38P = {1.0}p38
p53Degradation {1.0}Mdm2p53 = {1.0}Mdm2
p53Mdm2IndepDegradation1 {1.0}p53P = {1.0}$Sink
p53Mdm2IndepDegradation2 {1.0}p53 = {1.0}$Sink
p53Synthesis {1.0}p53mRNA = {1.0}p53 + {1.0}p53mRNA
p53dephosorylation {1.0}p53P = {1.0}p53
p53mRNADegradation {1.0}p53mRNA = {1.0}$Sink
p53mRNASynthesis {1.0}$Source = {1.0}p53mRNA
p53phoshorylation {1.0}p53 + {1.0}ATMA = {1.0}p53P + {1.0}ATMA
end reactions

begin rate equations
ATMInactivation = kinactATM*ATMA[t]
ATMactivation = kactATM*ATMI[t]*damDNA[t]
DNAdamage = kdam*IR[t]
DNArepair = krepair*damDNA[t]
GADD45activation2 = kGADD45*p21[t]
GADD45degradation = kdegGADD45*GADD45[t]
Mdm2Degradation = kdegMdm2*Mdm2[t]
Mdm2Pdegradation = kdegATMMdm2*Mdm2P[t]
Mdm2Synthesis = ksynMdm2*Mdm2mRNA[t]
Mdm2dephosorylation = kdephosMdm2*Mdm2P[t]
Mdm2mRNADegradation = kdegMdm2mRNA*Mdm2mRNA[t]
Mdm2mRNASynthesis1 = ksynMdm2mRNA*p53[t]
Mdm2mRNASynthesis2 = ksynMdm2mRNA*p53P[t]
Mdm2phoshorylation = kphosMdm2*ATMA[t]*Mdm2[t]
P53Mdm2Binding = kbinMdm2p53*Mdm2[t]*p53[t]
P53Mdm2Release = krelMdm2p53*Mdm2p53[t]
ROSDNAdamage = kdamROS*ROS[t]
ROSgenerationP38 = kgenROSp38*kp38ROS*p38P[t]
ROSremoval = kremROS*ROS[t]
basalROSDNAdamage = kdamBasalROS*basalROS[t]
p21Synthesis1 = ksynp21step1*p21mRNA[t]
p21Synthesis2 = ksynp21step2*p21step1[t]
p21Synthesis3 = ksynp21step3*p21step2[t]
p21degradation = kdegp21*p21[t]
p21mRNADegradation = kdegp21mRNA*p21mRNA[t]
p21mRNASynthesis1 = ksynp21mRNAp53*p53[t]
p21mRNASynthesis2 = ksynp21mRNAp53P*p53P[t]
p38activation = kphosp38*GADD45[t]*p38[t]
p38inactivation = kdephosp38*p38P[t]
p53Degradation = kdegp53*Mdm2p53[t]
p53Mdm2IndepDegradation1 = kdegp53mdm2ind*p53P[t]
p53Mdm2IndepDegradation2 = kdegp53mdm2ind*p53[t]
p53Synthesis = ksynp53*p53mRNA[t]
p53dephosorylation = kdephosp53*p53P[t]
p53mRNADegradation = kdegp53mRNA*p53mRNA[t]
p53mRNASynthesis = ksynp53mRNA*Source
p53phoshorylation = kphosp53*ATMA[t]*p53[t]
end rate equations

begin parameters
kGADD45 = "4e-06"
kactATM = "2e-05"
kbinMdm2p53 = 0.001155
kdam = 0.007
kdamBasalROS = "1e-09"
kdamROS = "1e-05"
kdegATMMdm2 = 0.0004
kdegGADD45 = "1e-05"
kdegMdm2 = 0.000433
kdegMdm2mRNA = 0.0001
kdegp21 = 0.00019
kdegp21mRNA = "2.4e-05"
kdegp53 = 0.000825
kdegp53mRNA = 0.0001
kdegp53mdm2ind = "8.25e-07"
kdephosMdm2 = 0.5
kdephosp38 = 0.1
kdephosp53 = 0.5
kgenROSp38 = 0.00045
kinactATM = 0.0005
kp38ROS = 1.0
kphosMdm2 = 2.0
kphosp38 = 0.008
kphosp53 = 0.006
krelMdm2p53 = "1.155e-06"
kremROS = 0.000383
krepair = "6e-05"
ksynMdm2 = 0.000495
ksynMdm2mRNA = 0.0001
ksynp21mRNAp53 = "6e-08"
ksynp21mRNAp53P = "6e-06"
ksynp21step1 = 0.0004
ksynp21step2 = "4e-05"
ksynp21step3 = "4e-05"
ksynp53 = 0.006
ksynp53mRNA = 0.001
Sink = 1.0
Source = 1.0
cell = 1.0
end parameters

begin initial conditions
ATMA[0] = ATMAi
ATMI[0] = ATMIi
GADD45[0] = GADD45i
IR[0] = IRi
Mdm2[0] = Mdm2i
Mdm2P[0] = Mdm2Pi
Mdm2mRNA[0] = Mdm2mRNAi
Mdm2p53[0] = Mdm2p53i
ROS[0] = ROSi
basalROS[0] = basalROSi
damDNA[0] = damDNAi
p21[0] = p21i
p21basal[0] = p21basali
p21mRNA[0] = p21mRNAi
p21step1[0] = p21step1i
p21step2[0] = p21step2i
p38[0] = p38i
p38P[0] = p38Pi
p53[0] = p53i
p53P[0] = p53Pi
p53mRNA[0] = p53mRNAi
end initial conditions

begin initial values
ATMAi = 0.0
ATMIi = 200.0
GADD45i = 0.0
IRi = 0.0
Mdm2i = 5.0
Mdm2Pi = 0.0
Mdm2mRNAi = 10.0
Mdm2p53i = 95.0
ROSi = 0.0
basalROSi = 10.0
damDNAi = 0.0
p21i = 0.0
p21basali = 7.0
p21mRNAi = 1.0
p21step1i = 0.0
p21step2i = 0.0
p38i = 100.0
p38Pi = 0.0
p53i = 5.0
p53Pi = 0.0
p53mRNAi = 10.0
end initial values

begin assignment rules
end assignment rules

begin function definitions
end function definitions

begin events
stopp38ROS = (t >= 691200, {kp38ROS -> 0.6}, 0)
stressCell = (t >= 172800, {IR[t] -> 200}, 0)
stopStress = (t >= 172860, {IR[t] -> 0}, 0)
end events

begin process annotations
end process annotations

begin species annotations
end species annotations

begin units
end units