// Created by libAntimony v2.8.0 model *Hsp70Model() // Compartments and Species: compartment cytosol, nucleus; substanceOnly species NatP in cytosol, MisP in cytosol, Hsp70 in cytosol; substanceOnly species Hsp90 in cytosol, Hsp70_dam in cytosol, Hsp90_dam in cytosol; substanceOnly species Hsp90_Proteasome in cytosol, Hsp70_Proteasome in cytosol; substanceOnly species Hsp70Client in cytosol, Hsp90Client in cytosol, Hsp70_Hsp70Client in cytosol; substanceOnly species Hsp90_Hsp90Client in cytosol, Akt in cytosol, Akt_Hsp90 in cytosol; substanceOnly species CHIP in cytosol, Akt_CHIP_Hsp90 in cytosol, Akt_Proteasome in cytosol; substanceOnly species Hsf1 in cytosol, Hsf1_Hsp90 in cytosol, Hsp90_MisP in cytosol; substanceOnly species Hsp70_MisP in cytosol, Hsf1_Hsf1_Hsf1 in nucleus; substanceOnly species Hsf1_Hsf1_Hsf1_P in nucleus, Hsf1_Hsf1 in cytosol; substanceOnly species HSEHsp70 in nucleus, HSEHsp90 in nucleus, HSEHsp70_Hsf1_Hsf1_Hsf1 in nucleus; substanceOnly species HSEHsp70_Hsf1_Hsf1_Hsf1_P in nucleus, HSEHsp90_Hsf1_Hsf1_Hsf1 in nucleus; substanceOnly species HSEHsp90_Hsf1_Hsf1_Hsf1_P in nucleus, Jnk in cytosol; substanceOnly species Jnk_P in cytosol, Ppx in cytosol, Mkp1 in cytosol; substanceOnly species Mkp1_P in cytosol, Mkp1_Proteasome in cytosol, Hsp70_Ppx in cytosol; substanceOnly species Pkc in cytosol, p38 in cytosol, p38_P in cytosol; substanceOnly species Proteasome in cytosol, MisP_Proteasome in cytosol; substanceOnly species AggP in cytosol, SeqAggP in cytosol, AggP_Proteasome in cytosol; substanceOnly species ROS in cytosol, $ATP in cytosol, $ADP in cytosol; substanceOnly species $Source in cytosol, $Sink in cytosol, p38Death in cytosol; substanceOnly species JNKDeath in cytosol, PIDeath in cytosol, CellDeath in cytosol; // Assignment Rules: tot_Hsp90 := Hsp90 + Hsp90_dam + Hsp90_Proteasome + Hsp90_Hsp90Client + Akt_Hsp90 + Akt_CHIP_Hsp90 + Hsf1_Hsp90 + Hsp90_MisP; tot_Hsp70 := Hsp70 + Hsp70_dam + Hsp70_Proteasome + Hsp70_Hsp70Client + Hsp70_MisP + Hsp70_Ppx; tot_MisP := MisP + Hsp70_MisP + Hsp90_MisP; // Reactions: ProteinSynthesis: $Source => NatP; ksynNatP*Source*kalive; Misfolding: NatP + ROS => MisP + ROS; kmisfold*NatP*ROS*kalive; Hsp90MisPBinding: MisP + Hsp90 => Hsp90_MisP; kbinHspMisp*MisP*Hsp90*kalive; Hsp90unsuccessulRefolding: Hsp90_MisP => MisP + Hsp90; krelHspMisp*Hsp90_MisP*kalive; Hsp90refolding: Hsp90_MisP + $ATP => Hsp90 + NatP + $ADP; (krefold*Hsp90_MisP*kalive*ATP)/(5000 + ATP); Hsp70MisPBinding: MisP + Hsp70 => Hsp70_MisP; kbinHspMisp*MisP*Hsp70*kalive; Hsp70unsuccessulRefolding: Hsp70_MisP => MisP + Hsp70; krelHspMisp*Hsp70_MisP*kalive; Hsp70refolding: Hsp70_MisP + $ATP => Hsp70 + NatP + $ADP; (krefold*Hsp70_MisP*kalive*ATP)/(5000 + ATP); Hsp70ClientBinding: Hsp70 + Hsp70Client => Hsp70_Hsp70Client; kbinHsp70client*Hsp70*Hsp70Client*kalive; Hsp70ClientRelease: Hsp70_Hsp70Client => Hsp70 + Hsp70Client; krelHsp70client*Hsp70_Hsp70Client*kalive; Hsp90ClientBinding: Hsp90 + Hsp90Client => Hsp90_Hsp90Client; kbinHsp90client*Hsp90*Hsp90Client*kalive; Hsp90ClientRelease: Hsp90_Hsp90Client => Hsp90 + Hsp90Client; krelHsp90client*Hsp90_Hsp90Client*kalive; Hsp90HSF1Binding: Hsp90 + Hsf1 => Hsf1_Hsp90; kbinHsf1Hsp90*Hsp90*Hsf1*kalive; Hsp90HSF1Release: Hsf1_Hsp90 => Hsp90 + Hsf1; krelHsf1Hsp90*Hsf1_Hsp90*kalive; dimerisation: 2Hsf1 => Hsf1_Hsf1; ((Hsf1 - 1)*kdimerHsf1*kalive*Hsf1)/2; trimerisation: Hsf1 + Hsf1_Hsf1 => Hsf1_Hsf1_Hsf1; ktrimerHsf1*Hsf1*Hsf1_Hsf1*kalive; deTrimerisation: Hsf1_Hsf1_Hsf1 => Hsf1 + Hsf1_Hsf1; kdetrimerHsf1*Hsf1_Hsf1_Hsf1*kalive; deDimerisation: Hsf1_Hsf1 => 2Hsf1; kdedimerHsf1*Hsf1_Hsf1*kalive; HSE70TriHBinding: Hsf1_Hsf1_Hsf1 + HSEHsp70 => HSEHsp70_Hsf1_Hsf1_Hsf1; kbinHSEHsf1*HSEHsp70*Hsf1_Hsf1_Hsf1*kalive; HSE70TriHRelease: HSEHsp70_Hsf1_Hsf1_Hsf1 => HSEHsp70 + Hsf1_Hsf1_Hsf1; krelHSEHsf1*HSEHsp70_Hsf1_Hsf1_Hsf1*kalive; HSE90TriHBinding: Hsf1_Hsf1_Hsf1 + HSEHsp90 => HSEHsp90_Hsf1_Hsf1_Hsf1; kbinHSEHsf1*HSEHsp90*Hsf1_Hsf1_Hsf1*kalive; HSE90TriHRelease: HSEHsp90_Hsf1_Hsf1_Hsf1 => HSEHsp90 + Hsf1_Hsf1_Hsf1; krelHSEHsf1*HSEHsp90_Hsf1_Hsf1_Hsf1*kalive; Hsf1_Hsf1_Hsf1Phosphorylation: Hsf1_Hsf1_Hsf1 + Pkc => Hsf1_Hsf1_Hsf1_P + Pkc; kphosHsf1*Hsf1_Hsf1_Hsf1*Pkc*kalive; Hsf1_Hsf1_Hsf1DePhosphorylation: Hsf1_Hsf1_Hsf1_P + Hsp70_Ppx => Hsf1_Hsf1_Hsf1 + Hsp70_Ppx; kdephosHsf1*Hsf1_Hsf1_Hsf1_P*Hsp70_Ppx*kalive; HSE70PhosTriHBinding: Hsf1_Hsf1_Hsf1_P + HSEHsp70 => HSEHsp70_Hsf1_Hsf1_Hsf1_P; kbinHSEPhosTriH*HSEHsp70*Hsf1_Hsf1_Hsf1_P*kalive; HSE70PhosTriHRelease: HSEHsp70_Hsf1_Hsf1_Hsf1_P => Hsf1_Hsf1_Hsf1_P + HSEHsp70; krelHSEPhosTriH*HSEHsp70_Hsf1_Hsf1_Hsf1_P*kalive; HSE90PhosTriHBinding: Hsf1_Hsf1_Hsf1_P + HSEHsp90 => HSEHsp90_Hsf1_Hsf1_Hsf1_P; kbinHSEPhosTriH*HSEHsp90*Hsf1_Hsf1_Hsf1_P*kalive; HSE90PhosTriHRelease: HSEHsp90_Hsf1_Hsf1_Hsf1_P => Hsf1_Hsf1_Hsf1_P + HSEHsp90; krelHSEPhosTriH*HSEHsp90_Hsf1_Hsf1_Hsf1_P*kalive; Hsp90BasalSynthesis: $Source => Hsp90; kbasalsynHsp90*kalive; Hsp90Upregulation: HSEHsp90_Hsf1_Hsf1_Hsf1_P => HSEHsp90_Hsf1_Hsf1_Hsf1_P + Hsp90; kupregHsp*HSEHsp90_Hsf1_Hsf1_Hsf1_P*kalive; Hsp90ProteasomeBinding: Hsp90 + Proteasome => Hsp90_Proteasome; kbinHsp90Prot*Hsp90*Proteasome*kalive; Hsp90Degradation: Hsp90_Proteasome + $ATP => Proteasome + $ADP; (kdegHsp90*Hsp90_Proteasome*kalive*ATP)/(5000 + ATP); Hsp70BasalSynthesis: $Source => Hsp70; kbasalsynHsp70*kalive; Hsp70Upregulation: HSEHsp70_Hsf1_Hsf1_Hsf1_P => HSEHsp70_Hsf1_Hsf1_Hsf1_P + Hsp70; kupregHsp*HSEHsp70_Hsf1_Hsf1_Hsf1_P*kalive; Hsp70ProteasomeBinding: Hsp70 + Proteasome => Hsp70_Proteasome; kbinHsp70Prot*Hsp70*Proteasome*kalive; Hsp70Degradation: Hsp70_Proteasome + $ATP => Proteasome + $ADP; (kdegHsp70*Hsp70_Proteasome*kalive*ATP)/(5000 + ATP); MisPProteasomeBinding1: Hsp70_MisP + Proteasome => MisP_Proteasome + Hsp70; kbinMisPProt*Hsp70_MisP*Proteasome*kalive; MisPProteasomeBinding2: Hsp90_MisP + Proteasome => MisP_Proteasome + Hsp90; kbinMisPProt*Hsp90_MisP*Proteasome*kalive; MisPDegradation: MisP_Proteasome + $ATP => Proteasome + $ADP; (kdegMisP*MisP_Proteasome*kalive*ATP)/(5000 + ATP); radicalFormation: $Source => ROS; kgenROS*Source*kalive; radicalScavenging: ROS => $Sink; kremROS*ROS*kalive; Hsp70_PpxBinding: Hsp70 + Ppx => Hsp70_Ppx; kbinHsp70Ppx*Hsp70*Ppx*kalive; Hsp70_PPXRelease: Hsp70_Ppx => Hsp70 + Ppx; krelHsp70Ppx*Hsp70_Ppx*kalive; JnkPhosphorylation: ROS + Jnk => ROS + Jnk_P; kphosJnk*Jnk*ROS*kalive; JNKDephosphorylatioByMkp1: Jnk_P + Mkp1_P => Jnk + Mkp1_P; kdephosJnkMkp1*Jnk_P*Mkp1_P*kalive; p38Phosphorylation: ROS + p38 => ROS + p38_P; kphosp38*ROS*p38*kalive; p38DePhosphorylationByMkp1: p38_P + Mkp1_P => p38 + Mkp1_P; kdephosp38Mkp1*p38_P*Mkp1_P*kalive; Aggregation1: 2MisP => AggP; kagg*MisP*(MisP - 1)*0.5*kalive; SequesteringOfAggregate: MisP + AggP => SeqAggP; kagg*MisP*AggP*kalive; InclusionGrowth: SeqAggP + MisP => 2SeqAggP; kseqagg*SeqAggP*MisP*kalive; ProteasomeInhibtion: AggP + Proteasome => AggP_Proteasome; kbinAggPProt*AggP*Proteasome*kalive; ROSgenerationSmallAggP: AggP => AggP + ROS; kgenROSAggP*AggP*kalive; ROSgenerationAggPProteasome: AggP_Proteasome => AggP_Proteasome + ROS; kgenROSAggP*AggP_Proteasome*kalive; AktSynthesis: $Source => Akt; ksynAkt*Source*kalive; Hsp90AktBinding: Hsp90 + Akt => Akt_Hsp90; kbinAktHsp90*Hsp90*Akt*kalive; Hsp90AktRelease: Akt_Hsp90 => Akt + Hsp90; krelAktHsp90*Akt_Hsp90*kalive; CHIPbinding: CHIP + Akt_Hsp90 => Akt_CHIP_Hsp90; kbinCHIP*CHIP*Akt_Hsp90*kalive; CHIPrelease: Akt_CHIP_Hsp90 => CHIP + Akt_Hsp90; krelCHIP*Akt_CHIP_Hsp90*kalive; AktProteasomeBinding: Akt_CHIP_Hsp90 + Proteasome => Akt_Proteasome + CHIP + Hsp90; kbinAktProt*Akt_CHIP_Hsp90*Proteasome*kalive; AktProteasomeRelease: Akt_Proteasome => Akt + Proteasome; krelAktProt*Akt_Proteasome*kalive; AktDegradation: Akt_Proteasome + $ATP => Proteasome + $ADP; (kdegAkt*Akt_Proteasome*kalive*ATP)/(5000 + ATP); Mkp1Synthesis: $Source => Mkp1; ksynMkp1*Source*kalive; Mkp1ProteasomeBinding: Mkp1 + Proteasome => Mkp1_Proteasome; kbinMkp1Prot*Mkp1*Proteasome*kalive; Mkp1Degradation: Mkp1_Proteasome + $ATP => Proteasome + $ADP; (kdegMkp1*Mkp1_Proteasome*kalive*ATP)/(5000 + ATP); Mkp1Phosphorylation: Mkp1 + Hsp70 => Mkp1_P + Hsp70; kphosMkp1*Mkp1*Hsp70*kalive; Mkp1Dephosphorylation: Mkp1_P + ROS => Mkp1 + ROS; kdephosMkp1*Mkp1_P*ROS*kalive; p38ROSproduction: p38_P => p38_P + ROS; kgenROSp38*p38_P*kalive*kp38act; Hsp70Damage: Hsp70 + ROS => Hsp70_dam + ROS; kdamHsp*Hsp70*ROS*kalive; Hsp90Damage: Hsp90 + ROS => Hsp90_dam + ROS; kdamHsp*Hsp90*ROS*kalive; Hsp70DamProteasomeBinding: Hsp70_dam + Proteasome => Hsp70_Proteasome; kbinHsp70Prot*Hsp70_dam*Proteasome*kalive; Hsp90DamProteasomeBinding: Hsp90_dam + Proteasome => Hsp90_Proteasome; kbinHsp90Prot*Hsp90_dam*Proteasome*kalive; Hsp70DamAggregation1: 2Hsp70_dam => AggP; kagg*Hsp70_dam*(Hsp70_dam - 1)*0.5*kalive; Hsp70DamInclusionFormation: Hsp70_dam + AggP => SeqAggP; kagg*Hsp70_dam*AggP*kalive; Hsp90DamAggregation: 2Hsp90_dam => AggP; kagg*Hsp90_dam*(Hsp90_dam - 1)*0.5*kalive; Hsp90DamInclusionFormation: Hsp90_dam + AggP => SeqAggP; kagg*Hsp90_dam*AggP*kalive; Hsp70DamSequestering: Hsp70_dam + SeqAggP => 2SeqAggP; kseqagg*Hsp70_dam*SeqAggP*kalive; Hsp90DamSequestering: Hsp90_dam + SeqAggP => 2SeqAggP; kseqagg*Hsp90_dam*SeqAggP*kalive; p38CellDeath: p38_P => p38_P + p38Death + CellDeath; kp38death*p38_P*kalive*kp38act; JnkCellDeath: Jnk_P => Jnk_P + JNKDeath + CellDeath; kJnkdeath*Jnk_P*kalive; PICellDeath: AggP_Proteasome => AggP_Proteasome + PIDeath + CellDeath; kPIdeath*AggP_Proteasome*kalive; // Events: DeathOfCell: at CellDeath >= 1: kalive = 0; // Species initializations: NatP = 17600/cytosol; MisP = 0; Hsp70 = 1400/cytosol; Hsp90 = 1850/cytosol; Hsp70_dam = 0; Hsp90_dam = 0; Hsp90_Proteasome = 0; Hsp70_Proteasome = 0; Hsp70Client = 490/cytosol; Hsp90Client = 590/cytosol; Hsp70_Hsp70Client = 10/cytosol; Hsp90_Hsp90Client = 10/cytosol; Akt = 340/cytosol; Akt_Hsp90 = 30/cytosol; CHIP = 255/cytosol; Akt_CHIP_Hsp90 = 80/cytosol; Akt_Proteasome = 0; Hsf1 = 5/cytosol; Hsf1_Hsp90 = 95/cytosol; Hsp90_MisP = 470/cytosol; Hsp70_MisP = 410/cytosol; Hsf1_Hsf1_Hsf1 = 0; Hsf1_Hsf1_Hsf1_P = 0; Hsf1_Hsf1 = 0; HSEHsp70 = 2/nucleus; HSEHsp90 = 2/nucleus; HSEHsp70_Hsf1_Hsf1_Hsf1 = 0; HSEHsp70_Hsf1_Hsf1_Hsf1_P = 0; HSEHsp90_Hsf1_Hsf1_Hsf1 = 0; HSEHsp90_Hsf1_Hsf1_Hsf1_P = 0; Jnk = 100/cytosol; Jnk_P = 0; Ppx = 0; Mkp1 = 0; Mkp1_P = 100/cytosol; Mkp1_Proteasome = 0; Hsp70_Ppx = 100/cytosol; Pkc = 100/cytosol; p38 = 100/cytosol; p38_P = 0; Proteasome = 500/cytosol; MisP_Proteasome = 0; AggP = 0; SeqAggP = 0; AggP_Proteasome = 0; ROS = 10/cytosol; ATP = 10000/cytosol; ADP = 1000/cytosol; Source = 1/cytosol; Sink = 1/cytosol; p38Death = 0; JNKDeath = 0; PIDeath = 0; CellDeath = 0; // Compartment initializations: cytosol = 1; nucleus = 1; // Variable initializations: kalive = 1; ksynNatP = 0.042; kmisfold = 2e-006; kbinMisPProt = 1e-007; kdegMisP = 0.01; kagg = 1e-008; kseqagg = 7e-007; kbinAggPProt = 1e-005; kbinHspMisp = 8e-006; krelHspMisp = 8e-005; krefold = 0.00055; kbinHsf1Hsp90 = 0.02; krelHsf1Hsp90 = 0.5; kdimerHsf1 = 8e-005; ktrimerHsf1 = 0.01; kdetrimerHsf1 = 0.5; kdedimerHsf1 = 0.5; kbinHSEHsf1 = 0.05; krelHSEHsf1 = 0.08; kupregHsp = 0.2; kbasalsynHsp70 = 0.008; kbasalsynHsp90 = 0.008; kbinHsp70Prot = 1.2e-008; kbinHsp90Prot = 1e-008; kdegHsp70 = 0.01; kdegHsp90 = 0.01; kgenROS = 0.01; kremROS = 0.001; kbinHsp70client = 0.0002; krelHsp70client = 5; kbinHsp90client = 0.0002; krelHsp90client = 5; kphosJnk = 0.02; kdephosJnkMkp1 = 0.05; kbinHsp70Ppx = 0.2; krelHsp70Ppx = 5; kphosHsf1 = 0.03; kdephosHsf1 = 0.01; kbinHSEPhosTriH = 0.1; krelHSEPhosTriH = 0.08; kphosp38 = 0.02; kdephosp38Mkp1 = 0.05; kgenROSAggP = 1e-006; ksynAkt = 0.0015; kbinAktHsp90 = 0.00037; krelAktHsp90 = 7; kbinAktProt = 6e-008; krelAktProt = 1e-008; kdegAkt = 0.01; kbinCHIP = 2e-007; krelCHIP = 1e-008; ksynMkp1 = 1e-005; kbinMkp1Prot = 9.6e-009; kdegMkp1 = 0.01; kphosMkp1 = 0.02; kdephosMkp1 = 0.001; kgenROSp38 = 0.0001; kdamHsp = 1e-008; kp38death = 1.5e-007; kJnkdeath = 1.5e-007; kPIdeath = 2e-008; kp38act = 1; // Other declarations: var kalive, kbinHsf1Hsp90, kgenROS, krelHsp90client, krelAktHsp90, kp38act; var tot_Hsp90, tot_Hsp70, tot_MisP; const cytosol, nucleus, ksynNatP, kmisfold, kbinMisPProt, kdegMisP, kagg; const kseqagg, kbinAggPProt, kbinHspMisp, krelHspMisp, krefold, krelHsf1Hsp90; const kdimerHsf1, ktrimerHsf1, kdetrimerHsf1, kdedimerHsf1, kbinHSEHsf1; const krelHSEHsf1, kupregHsp, kbasalsynHsp70, kbasalsynHsp90, kbinHsp70Prot; const kbinHsp90Prot, kdegHsp70, kdegHsp90, kremROS, kbinHsp70client, krelHsp70client; const kbinHsp90client, kphosJnk, kdephosJnkMkp1, kbinHsp70Ppx, krelHsp70Ppx; const kphosHsf1, kdephosHsf1, kbinHSEPhosTriH, krelHSEPhosTriH, kphosp38; const kdephosp38Mkp1, kgenROSAggP, ksynAkt, kbinAktHsp90, kbinAktProt, krelAktProt; const kdegAkt, kbinCHIP, krelCHIP, ksynMkp1, kbinMkp1Prot, kdegMkp1, kphosMkp1; const kdephosMkp1, kgenROSp38, kdamHsp, kp38death, kJnkdeath, kPIdeath; // Unit definitions: unit substance = item; end