begin name
tang1
end name

begin reactions
AggPProteasomeSequestering {1.0}AggPProteasome + {1.0}SeqAggP = {2.0}SeqAggP
MisPInclusionGrowth {1.0}MisP + {1.0}SeqAggP = {2.0}SeqAggP
MisPAggregation1 {2.0}MisP = {1.0}AggP1
MisPAggregation2 {1.0}MisP + {1.0}AggP1 = {1.0}AggP2
MisPAggregation3 {1.0}MisP + {1.0}AggP2 = {1.0}AggP3
MisPAggregation4 {1.0}MisP + {1.0}AggP3 = {1.0}AggP4
MisPAggregation5 {1.0}MisP + {1.0}AggP4 = {1.0}AggP5
MisPDegradation {1.0}MisPProteasome = {1.0}Proteasome
MisPDisaggregation1 {1.0}AggP1 = {2.0}MisP
MisPDisaggregation2 {1.0}AggP2 = {1.0}MisP + {1.0}AggP1
MisPDisaggregation3 {1.0}AggP3 = {1.0}MisP + {1.0}AggP2
MisPDisaggregation4 {1.0}AggP4 = {1.0}MisP + {1.0}AggP3
MisPDisaggregation5 {1.0}AggP5 = {1.0}MisP + {1.0}AggP4
MisPInclusionFormation {1.0}MisP + {1.0}AggP5 = {7.0}SeqAggP
MisPProteasomeBinding {1.0}MisP + {1.0}Proteasome = {1.0}MisPProteasome
MisPProteasomeRelease {1.0}MisPProteasome = {1.0}MisP + {1.0}Proteasome
MisPProteasomeSequestering {1.0}MisPProteasome + {1.0}SeqAggP = {2.0}SeqAggP
Misfolding {1.0}NatP + {1.0}ROS = {1.0}MisP + {1.0}ROS
P38DeathPathway {1.0}p38P = {1.0}p38P + {1.0}p38death
PIDeathPathway {1.0}AggPProteasome = {1.0}AggPProteasome + {1.0}PIdeath
PolyQAggregation1 {2.0}PolyQ + {1.0}ROS = {1.0}AggPolyQ1 + {1.0}ROS
PolyQAggregation2 {1.0}PolyQ + {1.0}AggPolyQ1 + {1.0}ROS = {1.0}AggPolyQ2 + {1.0}ROS
PolyQAggregation3 {1.0}PolyQ + {1.0}AggPolyQ2 + {1.0}ROS = {1.0}AggPolyQ3 + {1.0}ROS
PolyQAggregation4 {1.0}PolyQ + {1.0}AggPolyQ3 + {1.0}ROS = {1.0}AggPolyQ4 + {1.0}ROS
PolyQAggregation5 {1.0}PolyQ + {1.0}AggPolyQ4 + {1.0}ROS = {1.0}AggPolyQ5 + {1.0}ROS
PolyQDegradation {1.0}PolyQProteasome = {1.0}Proteasome
PolyQDisaggregation1 {1.0}AggPolyQ1 = {2.0}PolyQ
PolyQDisaggregation2 {1.0}AggPolyQ2 = {1.0}PolyQ + {1.0}AggPolyQ1
PolyQDisaggregation3 {1.0}AggPolyQ3 = {1.0}PolyQ + {1.0}AggPolyQ2
PolyQDisaggregation4 {1.0}AggPolyQ4 = {1.0}PolyQ + {1.0}AggPolyQ3
PolyQDisaggregation5 {1.0}AggPolyQ5 = {1.0}PolyQ + {1.0}AggPolyQ4
PolyQInclusionFormation {1.0}PolyQ + {1.0}AggPolyQ5 = {7.0}SeqAggP
PolyQInclusionGrowth {1.0}PolyQ + {1.0}SeqAggP = {2.0}SeqAggP
PolyQProteasomeSequestering {1.0}PolyQProteasome + {1.0}SeqAggP = {2.0}SeqAggP
ProteasomeInhibition1 {1.0}AggPolyQ1 + {1.0}Proteasome = {1.0}AggPProteasome
ProteasomeInhibition2 {1.0}AggPolyQ2 + {1.0}Proteasome = {1.0}AggPProteasome
ProteasomeInhibition3 {1.0}AggPolyQ3 + {1.0}Proteasome = {1.0}AggPProteasome
ProteasomeInhibition4 {1.0}AggPolyQ4 + {1.0}Proteasome = {1.0}AggPProteasome
ProteasomeInhibition5 {1.0}AggPolyQ5 + {1.0}Proteasome = {1.0}AggPProteasome
ProteasomeInhibitionAggP1 {1.0}AggP1 + {1.0}Proteasome = {1.0}AggPProteasome
ProteasomeInhibitionAggP2 {1.0}AggP2 + {1.0}Proteasome = {1.0}AggPProteasome
ProteasomeInhibitionAggP3 {1.0}AggP3 + {1.0}Proteasome = {1.0}AggPProteasome
ProteasomeInhibitionAggP4 {1.0}AggP4 + {1.0}Proteasome = {1.0}AggPProteasome
ProteasomeInhibitionAggP5 {1.0}AggP5 + {1.0}Proteasome = {1.0}AggPProteasome
ProteinSynthesis {1.0}$Source = {1.0}NatP
ROSgenerationAggPProteasome {1.0}AggPProteasome = {1.0}AggPProteasome + {1.0}ROS
ROSgenerationBasal {1.0}$Source = {1.0}ROS
ROSgenerationSeqAggP {1.0}SeqAggP = {1.0}SeqAggP + {1.0}ROS
ROSgenerationSmallAggP1 {1.0}AggP1 = {1.0}AggP1 + {1.0}ROS
ROSgenerationSmallAggP2 {1.0}AggP2 = {1.0}AggP2 + {1.0}ROS
ROSgenerationSmallAggP3 {1.0}AggP3 = {1.0}AggP3 + {1.0}ROS
ROSgenerationSmallAggP4 {1.0}AggP4 = {1.0}AggP4 + {1.0}ROS
ROSgenerationSmallAggP5 {1.0}AggP5 = {1.0}AggP5 + {1.0}ROS
ROSgenerationSmallAggPolyQ1 {1.0}AggPolyQ1 = {1.0}AggPolyQ1 + {1.0}ROS
ROSgenerationSmallAggPolyQ2 {1.0}AggPolyQ2 = {1.0}AggPolyQ2 + {1.0}ROS
ROSgenerationSmallAggPolyQ3 {1.0}AggPolyQ3 = {1.0}AggPolyQ3 + {1.0}ROS
ROSgenerationSmallAggPolyQ4 {1.0}AggPolyQ4 = {1.0}AggPolyQ4 + {1.0}ROS
ROSgenerationSmallAggPolyQ5 {1.0}AggPolyQ5 = {1.0}AggPolyQ5 + {1.0}ROS
ROSremoval {1.0}ROS = {1.0}$Sink
Refolding {1.0}MisP = {1.0}NatP
mRFPuDegradation {1.0}mRFPuProteasome = {1.0}Proteasome
mRFPuProteasomeBinding {1.0}mRFPu + {1.0}Proteasome = {1.0}mRFPuProteasome
mRFPuProteasomeRelease {1.0}mRFPuProteasome = {1.0}mRFPu + {1.0}Proteasome
mRFPuProteasomeSequestering {1.0}mRFPuProteasome + {1.0}SeqAggP = {2.0}SeqAggP
mRFPuSequestering {1.0}mRFPu + {1.0}SeqAggP = {2.0}SeqAggP
mRFPuSynthesis {1.0}$Source = {1.0}mRFPu
p38PROSGeneration {1.0}p38P = {1.0}p38P + {1.0}ROS
p38activation {1.0}ROS + {1.0}p38 = {1.0}ROS + {1.0}p38P
p38inactivation {1.0}p38P = {1.0}p38
polyQSynthesis {1.0}$Source = {1.0}PolyQ
polyqProteasomeBinding {1.0}PolyQ + {1.0}Proteasome = {1.0}PolyQProteasome
polyqProteasomeRelease {1.0}PolyQProteasome = {1.0}PolyQ + {1.0}Proteasome
end reactions

begin rate equations
AggPProteasomeSequestering = kalive*kseqAggPProt*AggPProteasome[t]*SeqAggP[t]
MisPInclusionGrowth = kalive*kseqMisP*MisP[t]*SeqAggP[t]
MisPAggregation1 = 0.5*kaggMisP*kalive*(-1 + MisP[t])*MisP[t]
MisPAggregation2 = kagg2MisP*kalive*AggP1[t]*MisP[t]
MisPAggregation3 = kagg2MisP*kalive*AggP2[t]*MisP[t]
MisPAggregation4 = kagg2MisP*kalive*AggP3[t]*MisP[t]
MisPAggregation5 = kagg2MisP*kalive*AggP4[t]*MisP[t]
MisPDegradation = kalive*kdegMisP*kproteff*MisPProteasome[t]
MisPDisaggregation1 = kalive*kdisaggMisP1*AggP1[t]
MisPDisaggregation2 = kalive*kdisaggMisP2*AggP2[t]
MisPDisaggregation3 = kalive*kdisaggMisP3*AggP3[t]
MisPDisaggregation4 = kalive*kdisaggMisP4*AggP4[t]
MisPDisaggregation5 = kalive*kdisaggMisP5*AggP5[t]
MisPInclusionFormation = kagg2MisP*kalive*AggP5[t]*MisP[t]
MisPProteasomeBinding = kalive*kbinMisPProt*MisP[t]*Proteasome[t]
MisPProteasomeRelease = kalive*krelMisPProt*MisPProteasome[t]
MisPProteasomeSequestering = kalive*kseqMisPProt*MisPProteasome[t]*SeqAggP[t]
Misfolding = kalive*kmisfold*NatP[t]*ROS[t]
P38DeathPathway = kalive*kp38act*kp38death*p38P[t]
PIDeathPathway = kalive*kPIdeath*AggPProteasome[t]
PolyQAggregation1 = (0.5*kaggPolyQ*kalive*(-1 + PolyQ[t])*PolyQ[t]*ROS[t]^2)/(100 + ROS[t]^2)
PolyQAggregation2 = (kaggPolyQ*kalive*AggPolyQ1[t]*PolyQ[t]*ROS[t]^2)/(100 + ROS[t]^2)
PolyQAggregation3 = (kaggPolyQ*kalive*AggPolyQ2[t]*PolyQ[t]*ROS[t]^2)/(100 + ROS[t]^2)
PolyQAggregation4 = (kaggPolyQ*kalive*AggPolyQ3[t]*PolyQ[t]*ROS[t]^2)/(100 + ROS[t]^2)
PolyQAggregation5 = (kaggPolyQ*kalive*AggPolyQ4[t]*PolyQ[t]*ROS[t]^2)/(100 + ROS[t]^2)
PolyQDegradation = kalive*kdegPolyQ*kproteff*PolyQProteasome[t]
PolyQDisaggregation1 = kalive*kdisaggPolyQ1*AggPolyQ1[t]
PolyQDisaggregation2 = kalive*kdisaggPolyQ2*AggPolyQ2[t]
PolyQDisaggregation3 = kalive*kdisaggPolyQ3*AggPolyQ3[t]
PolyQDisaggregation4 = kalive*kdisaggPolyQ4*AggPolyQ4[t]
PolyQDisaggregation5 = kalive*kdisaggPolyQ5*AggPolyQ5[t]
PolyQInclusionFormation = kaggPolyQ*kalive*AggPolyQ5[t]*PolyQ[t]
PolyQInclusionGrowth = kalive*kseqPolyQ*PolyQ[t]*SeqAggP[t]
PolyQProteasomeSequestering = kalive*kseqPolyQProt*PolyQProteasome[t]*SeqAggP[t]
ProteasomeInhibition1 = kalive*kinhprot*AggPolyQ1[t]*Proteasome[t]
ProteasomeInhibition2 = kalive*kinhprot*AggPolyQ2[t]*Proteasome[t]
ProteasomeInhibition3 = kalive*kinhprot*AggPolyQ3[t]*Proteasome[t]
ProteasomeInhibition4 = kalive*kinhprot*AggPolyQ4[t]*Proteasome[t]
ProteasomeInhibition5 = kalive*kinhprot*AggPolyQ5[t]*Proteasome[t]
ProteasomeInhibitionAggP1 = kalive*kinhprot*AggP1[t]*Proteasome[t]
ProteasomeInhibitionAggP2 = kalive*kinhprot*AggP2[t]*Proteasome[t]
ProteasomeInhibitionAggP3 = kalive*kinhprot*AggP3[t]*Proteasome[t]
ProteasomeInhibitionAggP4 = kalive*kinhprot*AggP4[t]*Proteasome[t]
ProteasomeInhibitionAggP5 = kalive*kinhprot*AggP5[t]*Proteasome[t]
ProteinSynthesis = kalive*ksynNatP*Source
ROSgenerationAggPProteasome = kalive*kgenROSAggP*AggPProteasome[t]
ROSgenerationBasal = kalive*kgenROS*Source
ROSgenerationSeqAggP = kalive*kgenROSSeqAggP*SeqAggP[t]
ROSgenerationSmallAggP1 = kalive*kgenROSAggP*AggP1[t]
ROSgenerationSmallAggP2 = kalive*kgenROSAggP*AggP2[t]
ROSgenerationSmallAggP3 = kalive*kgenROSAggP*AggP3[t]
ROSgenerationSmallAggP4 = kalive*kgenROSAggP*AggP4[t]
ROSgenerationSmallAggP5 = kalive*kgenROSAggP*AggP5[t]
ROSgenerationSmallAggPolyQ1 = kalive*kgenROSAggP*AggPolyQ1[t]
ROSgenerationSmallAggPolyQ2 = kalive*kgenROSAggP*AggPolyQ2[t]
ROSgenerationSmallAggPolyQ3 = kalive*kgenROSAggP*AggPolyQ3[t]
ROSgenerationSmallAggPolyQ4 = kalive*kgenROSAggP*AggPolyQ4[t]
ROSgenerationSmallAggPolyQ5 = kalive*kgenROSAggP*AggPolyQ5[t]
ROSremoval = kalive*kremROS*ROS[t]
Refolding = kalive*krefold*MisP[t]
mRFPuDegradation = kalive*kdegmRFPu*kproteff*mRFPuProteasome[t]
mRFPuProteasomeBinding = kalive*kbinmRFPu*mRFPu[t]*Proteasome[t]
mRFPuProteasomeRelease = kalive*krelmRFPu*mRFPuProteasome[t]
mRFPuProteasomeSequestering = kalive*kseqmRFPuProt*mRFPuProteasome[t]*SeqAggP[t]
mRFPuSequestering = kalive*kseqmRFPu*mRFPu[t]*SeqAggP[t]
mRFPuSynthesis = kalive*ksynmRFPu*Source
p38PROSGeneration = kalive*kgenROSp38*kp38act*p38P[t]
p38activation = kactp38*kalive*p38[t]*ROS[t]
p38inactivation = kalive*kinactp38*p38P[t]
polyQSynthesis = kalive*ksynPolyQ*Source
polyqProteasomeBinding = kalive*kbinPolyQ*PolyQ[t]*Proteasome[t]
polyqProteasomeRelease = kalive*krelPolyQ*PolyQProteasome[t]
end rate equations

begin parameters
kPIdeath = "2.5e-08"
kactp38 = "5e-06"
kagg2MisP = "1e-10"
kaggMisP = "1e-11"
kaggPolyQ = "5e-08"
kalive = 1.0
kbinMisPProt = "5e-08"
kbinPolyQ = "5e-08"
kbinmRFPu = "5e-07"
kdegMisP = 0.01
kdegPolyQ = 0.0025
kdegmRFPu = 0.005
kdisaggMisP1 = "5e-07"
kdisaggMisP2 = "4e-07"
kdisaggMisP3 = "3e-07"
kdisaggMisP4 = "2e-07"
kdisaggMisP5 = "1e-07"
kdisaggPolyQ1 = "5e-07"
kdisaggPolyQ2 = "4e-07"
kdisaggPolyQ3 = "3e-07"
kdisaggPolyQ4 = "2e-07"
kdisaggPolyQ5 = "1e-07"
kgenROS = 0.0017
kgenROSAggP = "5e-06"
kgenROSSeqAggP = "1e-07"
kgenROSp38 = 0.0007
kinactp38 = 0.002
kinhprot = "5e-09"
kmisfold = "2e-06"
kp38act = 1.0
kp38death = "9e-08"
kproteff = 1.0
krefold = "8e-05"
krelMisPProt = "1e-08"
krelPolyQ = "1e-09"
krelmRFPu = "1e-08"
kremROS = 0.0002
kseqAggPProt = "5e-07"
kseqMisP = "1e-09"
kseqMisPProt = "5e-07"
kseqPolyQ = "8e-07"
kseqPolyQProt = "5e-07"
kseqmRFPu = "1e-10"
kseqmRFPuProt = "5e-07"
ksynNatP = 2.4
ksynPolyQ = 0.007
ksynmRFPu = 0.138
Sink = 1.0
Source = 1.0
cytosol = 1.0
end parameters

begin initial conditions
AggP1[0] = AggP1i
AggP2[0] = AggP2i
AggP3[0] = AggP3i
AggP4[0] = AggP4i
AggP5[0] = AggP5i
AggPProteasome[0] = AggPProteasomei
AggPolyQ1[0] = AggPolyQ1i
AggPolyQ2[0] = AggPolyQ2i
AggPolyQ3[0] = AggPolyQ3i
AggPolyQ4[0] = AggPolyQ4i
AggPolyQ5[0] = AggPolyQ5i
MisP[0] = MisPi
MisPProteasome[0] = MisPProteasomei
NatP[0] = NatPi
PIdeath[0] = PIdeathi
PolyQ[0] = PolyQi
PolyQProteasome[0] = PolyQProteasomei
Proteasome[0] = Proteasomei
ROS[0] = ROSi
SeqAggP[0] = SeqAggPi
mRFPu[0] = mRFPui
mRFPuProteasome[0] = mRFPuProteasomei
p38[0] = p38i
p38P[0] = p38Pi
p38death[0] = p38deathi
end initial conditions

begin initial values
AggP1i = 0.0
AggP2i = 0.0
AggP3i = 0.0
AggP4i = 0.0
AggP5i = 0.0
AggPProteasomei = 0.0
AggPolyQ1i = 0.0
AggPolyQ2i = 0.0
AggPolyQ3i = 0.0
AggPolyQ4i = 0.0
AggPolyQ5i = 0.0
MisPi = 0.0
MisPProteasomei = 0.0
NatPi = 19500.0
PIdeathi = 0.0
PolyQi = 1000.0
PolyQProteasomei = 0.0
Proteasomei = 1000.0
ROSi = 10.0
SeqAggPi = 0.0
mRFPui = 300.0
mRFPuProteasomei = 0.0
p38i = 100.0
p38Pi = 0.0
p38deathi = 0.0
end initial values

begin assignment rules
oligomers := AggPolyQ1[t] + AggPolyQ2[t] + AggPolyQ3[t] + AggPolyQ4[t] + AggPolyQ5[t]
end assignment rules

begin function definitions
end function definitions

begin events
PIcellDeath = (PIdeath[t] > 0, {kalive -> 0}, 0)
p38cellDeath = (p38death[t] > 0, {kalive -> 0}, 0)
end events

begin process annotations
end process annotations

begin species annotations
end species annotations

begin units
end units