AlternateErkSubnetwork.cpp Source File

00001 // AlternateErkSubnetwork.cpp: implementation of the CAlternateErkSubnetwork class.
00002 //
00004 
00005 #include "AlternateErkSubnetwork.h"
00006 
00008 // Construction/Destruction
00010 
00012 // Construction/Destruction
00014 
00015 // Changed stoichiometry on 3/8/01
00016 // - ERK and MEK are at CFactor
00017 // - NGFR = 10000, EGFR = 80000
00018 // - all else at 0.2*CFactor
00019 // - this network lacks the PI3K/Akt loop
00020 
00021 CAlternateErkSubnetwork::CAlternateErkSubnetwork()
00022 {
00023 // CFactor = #molecules/1uM
00024         double CFactor = 600000.0, SecToMin = 60.0;
00025 
00026         // 1
00027         Chemical *EGF = new Chemical(chemicals.size(), 0.0, "EGF");
00028         chemicals.push_back(EGF);
00029 
00030         // 2
00031         Chemical *NGF = new Chemical(chemicals.size(), 0.0, "NGF");
00032         chemicals.push_back(NGF);
00033 
00034         // 3 (ref - constraint on [EGFR]_T)
00035         Chemical *freeEGFReceptor = new Chemical(chemicals.size(), 80000, "freeEGFReceptor");
00036         chemicals.push_back(freeEGFReceptor);
00037 
00038         // 4 (ref)
00039         Chemical *boundEGFReceptor = new Chemical(chemicals.size(), 0.0, "boundEGFReceptor");
00040         chemicals.push_back(boundEGFReceptor);
00041 
00042         // 5 (ref)
00043         Chemical *freeNGFReceptor = new Chemical(chemicals.size(), 10000, "freeNGFReceptor");
00044         chemicals.push_back(freeNGFReceptor);
00045 
00046         // 6
00047         Chemical *boundNGFReceptor = new Chemical(chemicals.size(), 0.0, "boundNGFReceptor");
00048         chemicals.push_back(boundNGFReceptor);
00049 
00050         // 7
00051         Chemical *SosInactive = new Chemical(chemicals.size(), 0.2*CFactor, "SosInactive");
00052         chemicals.push_back(SosInactive);
00053                 
00054         // 8
00055         Chemical *SosActive = new Chemical(chemicals.size(), 0.0, "SosActive");
00056         chemicals.push_back(SosActive);
00057 
00058         // 9
00059         Chemical *P90RskInactive = new Chemical(chemicals.size(), 0.2*CFactor, "P90RskInactive");
00060         chemicals.push_back(P90RskInactive);
00061 
00062         // 10
00063 
00064         Chemical *P90RskActive = new Chemical(chemicals.size(), 0.0, "P90RskActive");
00065         chemicals.push_back(P90RskActive);
00066 
00067         // 11
00068         Chemical *RasInactive = new Chemical(chemicals.size(), 0.2*CFactor,"RasInactive");
00069         chemicals.push_back(RasInactive);
00070 
00071         // 12
00072         Chemical *RasActive = new Chemical(chemicals.size(), 0.0, "RasActive");
00073         chemicals.push_back(RasActive);
00074 
00075         // 13
00076         Chemical *RasGapActive = new Chemical(chemicals.size(), CFactor*0.2, "RasGapActive");
00077         chemicals.push_back(RasGapActive);
00078 
00079         
00080         // 14 (ref - constraint on [Raf1]_T = CFactor*0.003)
00081         Chemical *Raf1Inactive = new Chemical(chemicals.size(), CFactor*0.2, "Raf1Inactive");
00082         chemicals.push_back(Raf1Inactive);
00083                 
00084         // 15 (ref)
00085         Chemical *Raf1Active = new Chemical(chemicals.size(), 0.0, "Raf1Active");
00086         chemicals.push_back(Raf1Active);
00087 
00088         // 16 (ref- constraint on [BRaf]_T = CFactor*0.003)
00089         Chemical *BRafInactive = new Chemical(chemicals.size(), CFactor*0.2, "BRafInactive");
00090         chemicals.push_back(BRafInactive);
00091                 
00092         // 17 (ref)
00093         Chemical *BRafActive = new Chemical(chemicals.size(), 0.0, "BRafActive");
00094         chemicals.push_back(BRafActive);
00095 
00096         // 18 (ref - constraint on [Mek]_T)
00097         Chemical *MekInactive = new Chemical(chemicals.size(), CFactor, "MekInactive");
00098         chemicals.push_back(MekInactive);
00099 
00100         // 19 (ref)
00101         Chemical *MekActive = new Chemical(chemicals.size(), 0.0, "MekActive");
00102         chemicals.push_back(MekActive);
00103 
00104         // 20 (ref - constraint on [Erk]_T)
00105         Chemical *ErkInactive = new Chemical(chemicals.size(), CFactor,"ErkInactive");
00106         chemicals.push_back(ErkInactive);
00107 
00108         // 21 (ref)
00109         Chemical *ErkActive = new Chemical(chemicals.size(), 0.0, "ErkActive");
00110         chemicals.push_back(ErkActive);
00111 
00112         // 22
00113         Chemical *C3GInactive = new Chemical(chemicals.size(), 0.2*CFactor, "C3GInactive");
00114         chemicals.push_back(C3GInactive);
00115                 
00116         // 23
00117         Chemical *C3GActive = new Chemical(chemicals.size(), 0.0, "C3GActive");
00118         chemicals.push_back(C3GActive);
00119 
00120         // 24
00121         Chemical *Rap1Inactive = new Chemical(chemicals.size(), 0.2*CFactor, "Rap1Inactive");
00122         chemicals.push_back(Rap1Inactive);
00123 
00124         // 25
00125         Chemical *Rap1Active = new Chemical(chemicals.size(), 0.0, "Rap1Active");
00126         chemicals.push_back(Rap1Active);
00127 
00128         // 26
00129         Chemical *RapGapActive = new Chemical(chemicals.size(), 0.2*CFactor, "RapGapActive");
00130         chemicals.push_back(RapGapActive);
00131         
00132         // 27
00133         Chemical *PP2AActive = new Chemical(chemicals.size(), 0.2*CFactor, "PP2AActive");
00134         chemicals.push_back(PP2AActive);
00135 
00136         // 28 
00137         Chemical *Raf1PPtase = new Chemical(chemicals.size(), 0.2*CFactor, "Raf1PPtase");
00138         chemicals.push_back(Raf1PPtase);
00139 
00140 
00141         RateConstant *k_rb_EGF = new RateConstant(SecToMin*0.00001, "krbEGF");
00142         rateConstants.push_back(k_rb_EGF);
00143         RateConstant *k_ru_EGF = new RateConstant(SecToMin*0.01, "kruEGF");
00144         rateConstants.push_back(k_ru_EGF);
00145         RateConstant *k_rb_NGF = new RateConstant(SecToMin*0.00005, "krbNGF");
00146         rateConstants.push_back(k_rb_NGF);
00147         RateConstant *k_ru_NGF = new RateConstant(SecToMin*0.02, "kruNGF");
00148         rateConstants.push_back(k_ru_NGF);
00149 
00150         RateConstant *k_EGF = new RateConstant(SecToMin*0.2, "kEGF");
00151         rateConstants.push_back(k_EGF);
00152         RateConstant *Km_EGF = new RateConstant(CFactor*0.8333, "KmEGF");
00153         rateConstants.push_back(Km_EGF);
00154         RateConstant *k_NGF = new RateConstant(SecToMin*0.4, "kNGF");
00155         rateConstants.push_back(k_NGF);
00156         RateConstant *Km_NGF = new RateConstant(CFactor*0.8333, "KmNGF");
00157         rateConstants.push_back(Km_NGF);
00158 
00159         RateConstant *k_dSos = new RateConstant(0.01*SecToMin, "kdSos");
00160         rateConstants.push_back(k_dSos);
00161         RateConstant *Km_dSos = new RateConstant(100000.0, "KmdSos");
00162         rateConstants.push_back(Km_dSos);       
00163         RateConstant *k_Sos = new RateConstant(0.075*SecToMin, "kSos");
00164         rateConstants.push_back(k_Sos);
00165         RateConstant *Km_Sos = new RateConstant(0.25*CFactor, "KmSos");
00166         rateConstants.push_back(Km_Sos);
00167 
00168         RateConstant *k_RasGap = new RateConstant(0.2*SecToMin, "kRasGap");
00169         rateConstants.push_back(k_RasGap);
00170         RateConstant *Km_RasGap = new RateConstant(CFactor*1.0104, "KmRasGap");
00171         rateConstants.push_back(Km_RasGap);
00172         RateConstant *k_RasToRaf1 = new RateConstant(0.08*SecToMin, "kRasToRaf1");
00173         rateConstants.push_back(k_RasToRaf1);
00174         RateConstant *Km_RasToRaf1 = new RateConstant(150000.0, "KmRasToRaf1");
00175         rateConstants.push_back(Km_RasToRaf1);
00176         
00177         RateConstant *k_pRaf1 = new RateConstant(0.05*SecToMin, "kpRaf1");
00178         rateConstants.push_back(k_pRaf1);
00179         // (ref)
00180         RateConstant *Km_pRaf1 = new RateConstant(0.6*CFactor, "KmpRaf1");
00181         rateConstants.push_back(Km_pRaf1);
00182         RateConstant *k_pBRaf = new RateConstant(0.025*SecToMin, "kpBRaf");
00183         rateConstants.push_back(k_pBRaf);
00184         RateConstant *Km_pBRaf = new RateConstant(100000.0, "KmpBRaf");
00185         rateConstants.push_back(Km_pBRaf);
00186 
00187         RateConstant *k_dMek = new RateConstant(0.03*SecToMin, "kdMek");
00188         rateConstants.push_back(k_dMek);
00189         RateConstant *Km_dMek = new RateConstant(125000.0, "KmdMek");
00190         rateConstants.push_back(Km_dMek);
00191         
00192         RateConstant *k_pMek_Cytoplasmic = new RateConstant(0.01*SecToMin, "kpMekCytoplasmic");
00193         rateConstants.push_back(k_pMek_Cytoplasmic);
00194         // (ref)
00195         RateConstant *Km_pMek_Cytoplasmic = new RateConstant(125000.0, "KmpMekCytoplasmic");
00196         rateConstants.push_back(Km_pMek_Cytoplasmic);
00197         RateConstant *k_dErk = new RateConstant(0.01*SecToMin, "kdErk");
00198         rateConstants.push_back(k_dErk);
00199         RateConstant *Km_dErk = new RateConstant(300000.0, "KmdErk");
00200         rateConstants.push_back(Km_dErk);
00201         RateConstant *k_pP90Rsk = new RateConstant(0.01*SecToMin, "kpP90Rsk");
00202         rateConstants.push_back(k_pP90Rsk);
00203         RateConstant *Km_pP90Rsk = new RateConstant(300000.0, "KmpP90Rsk");
00204         rateConstants.push_back(Km_pP90Rsk);
00205                 
00206         
00207         RateConstant *k_C3G_NGF = new RateConstant(0.05*SecToMin, "kC3GNGF");
00208         rateConstants.push_back(k_C3G_NGF);
00209         RateConstant *Km_C3G_NGF = new RateConstant(200000.0, "KmC3GNGF");
00210         rateConstants.push_back(Km_C3G_NGF);
00211         RateConstant *k_C3G = new RateConstant(0.01*SecToMin, "kC3G"); 
00212         rateConstants.push_back(k_C3G);
00213         RateConstant *Km_C3G = new RateConstant(300000.0, "KmC3G");
00214         rateConstants.push_back(Km_C3G);
00215         RateConstant *k_RapGap = new RateConstant(0.002*SecToMin, "kRapGap");
00216         rateConstants.push_back(k_RapGap);
00217         RateConstant *Km_RapGap = new RateConstant(300000.0, "KmRapGap");
00218         rateConstants.push_back(Km_RapGap);
00219         RateConstant *k_Rap1ToBRaf = new RateConstant(0.05*SecToMin, "kRap1ToBRaf");
00220         rateConstants.push_back(k_Rap1ToBRaf);
00221         RateConstant *Km_Rap1ToBRaf = new RateConstant(300000.0, "KmRap1ToBRaf");
00222         rateConstants.push_back(Km_Rap1ToBRaf);
00223 
00224         RateConstant *k_dRaf1 = new RateConstant(0.1*SecToMin, "kdRaf1");
00225         rateConstants.push_back(k_dRaf1);
00226         RateConstant *Km_dRaf1 = new RateConstant(300000.0, "KmdRaf1");
00227         rateConstants.push_back(Km_dRaf1);
00228 
00229         RateConstant *k_dBRaf = new RateConstant(0.05*SecToMin, "kdBRaf");
00230         rateConstants.push_back(k_dBRaf);
00231         RateConstant *Km_dBRaf = new RateConstant(300000.0, "KmdBRaf");
00232         rateConstants.push_back(Km_dBRaf);
00233 
00234 
00235         ReceptorBindingReaction *EGFBindingReaction = new ReceptorBindingReaction(EGF, freeEGFReceptor, boundEGFReceptor, k_rb_EGF, "EGFBindingReaction");
00236         reactions.push_back(EGFBindingReaction);
00237         ReceptorUnbindingReaction *EGFUnbindingReaction = new ReceptorUnbindingReaction(boundEGFReceptor, freeEGFReceptor, EGF, k_ru_EGF, "EGFUnbindingReaction");
00238         reactions.push_back(EGFUnbindingReaction);
00239         ReceptorBindingReaction *NGFBindingReaction = new ReceptorBindingReaction(NGF, freeNGFReceptor, boundNGFReceptor, k_rb_NGF, "NGFBindingReaction");
00240         reactions.push_back(NGFBindingReaction);
00241         ReceptorUnbindingReaction *NGFUnbindingReaction = new ReceptorUnbindingReaction(boundNGFReceptor, freeNGFReceptor, NGF, k_ru_NGF, "NGFUnbindingReaction");
00242         reactions.push_back(NGFUnbindingReaction);
00243 
00244         MichaelisMentenPhosphorylationReaction *SosActivationByEGFReaction = new MichaelisMentenPhosphorylationReaction(boundEGFReceptor, SosInactive, SosActive, k_EGF, Km_EGF, "SosActivationbyEGFReaction");
00245         reactions.push_back(SosActivationByEGFReaction);
00246         MichaelisMentenPhosphorylationReaction *SosActivationByNGFReaction = new MichaelisMentenPhosphorylationReaction(boundNGFReceptor, SosInactive, SosActive, k_NGF, Km_NGF, "SosActivationbyNGFReaction");
00247         reactions.push_back(SosActivationByNGFReaction);
00248         MichaelisMentenDephosphorylationReaction *SosDeactivationReaction = new MichaelisMentenDephosphorylationReaction(P90RskActive, SosActive, SosInactive, k_dSos, Km_dSos, "SosDeactivationReaction");
00249         reactions.push_back(SosDeactivationReaction);
00250         MichaelisMentenGProteinActivationReaction *RasActivationReaction = new MichaelisMentenGProteinActivationReaction(SosActive, RasInactive, RasActive, k_Sos, Km_Sos, "RasActivationReaction");
00251         reactions.push_back(RasActivationReaction);
00252         
00253         MichaelisMentenGProteinDeactivationReaction *RasDeactivationReaction = new MichaelisMentenGProteinDeactivationReaction(RasGapActive, RasActive, RasInactive, k_RasGap, Km_RasGap, "RasDeactivationReaction");
00254         reactions.push_back(RasDeactivationReaction);
00255         MichaelisMentenProteinProteinActivationReaction *Raf1ByRasActivationReaction = new MichaelisMentenProteinProteinActivationReaction(RasActive, Raf1Inactive, Raf1Active, k_RasToRaf1, Km_RasToRaf1, "Raf1ByRasActivationReaction");
00256         reactions.push_back(Raf1ByRasActivationReaction);
00257 
00258         MichaelisMentenPhosphorylationReaction *MekbyRaf1ActivationReaction = new MichaelisMentenPhosphorylationReaction(Raf1Active, MekInactive, MekActive, k_pRaf1, Km_pRaf1, "MekbyRaf1ActivationReaction");
00259         reactions.push_back(MekbyRaf1ActivationReaction);
00260         MichaelisMentenPhosphorylationReaction *MekbyBRafActivationReaction = new MichaelisMentenPhosphorylationReaction(BRafActive, MekInactive, MekActive, k_pBRaf, Km_pBRaf, "MekbyBRafActivationReaction");
00261         reactions.push_back(MekbyBRafActivationReaction);
00262         MichaelisMentenPhosphorylationReaction *ErkActivationReaction = new MichaelisMentenPhosphorylationReaction(MekActive, ErkInactive, ErkActive, k_pMek_Cytoplasmic, Km_pMek_Cytoplasmic, "ErkActivationReaction");
00263         reactions.push_back(ErkActivationReaction);
00264 
00265         
00266         MichaelisMentenDephosphorylationReaction *MekDeactivationReaction = new MichaelisMentenDephosphorylationReaction(PP2AActive, MekActive, MekInactive, k_dMek, Km_dMek, "MekDeactivationReaction");
00267         reactions.push_back(MekDeactivationReaction);
00268         MichaelisMentenDephosphorylationReaction *ErkDeactivationReaction = new MichaelisMentenDephosphorylationReaction(PP2AActive, ErkActive, ErkInactive, k_dErk, Km_dErk, "ErkDeactivationReaction");
00269         reactions.push_back(ErkDeactivationReaction);
00270 
00271         MichaelisMentenDephosphorylationReaction *Raf1byPPtaseDeactivationReaction = new MichaelisMentenDephosphorylationReaction(Raf1PPtase, Raf1Active, Raf1Inactive, k_dRaf1, Km_dRaf1, "Raf1byPPtaseDeactivationReaction");
00272         reactions.push_back(Raf1byPPtaseDeactivationReaction);
00273 
00274         MichaelisMentenPhosphorylationReaction *P90RskActivationReaction = new MichaelisMentenPhosphorylationReaction(ErkActive, P90RskInactive, P90RskActive, k_pP90Rsk, Km_pP90Rsk, "P90RskActivationReaction");
00275         reactions.push_back(P90RskActivationReaction);
00276         
00277         MichaelisMentenPhosphorylationReaction *C3GActivationReaction = new MichaelisMentenPhosphorylationReaction(boundNGFReceptor, C3GInactive, C3GActive, k_C3G_NGF, Km_C3G_NGF, "C3GActivationReaction");
00278         reactions.push_back(C3GActivationReaction);
00279         MichaelisMentenGProteinActivationReaction *Rap1ActivationReaction = new MichaelisMentenGProteinActivationReaction(C3GActive, Rap1Inactive, Rap1Active, k_C3G, Km_C3G, "Rap1ActivationReaction");
00280         reactions.push_back(Rap1ActivationReaction);
00281         MichaelisMentenGProteinDeactivationReaction *Rap1DeactivationReaction = new MichaelisMentenGProteinDeactivationReaction(RapGapActive, Rap1Active, Rap1Inactive, k_RapGap, Km_RapGap, "Rap1DeactivationReaction");
00282         reactions.push_back(Rap1DeactivationReaction);
00283         MichaelisMentenProteinProteinActivationReaction *BRafByRap1ActivationReaction = new MichaelisMentenProteinProteinActivationReaction(Rap1Active, BRafInactive, BRafActive, k_Rap1ToBRaf, Km_Rap1ToBRaf, "BRafByRap1ActivationReaction");
00284         reactions.push_back(BRafByRap1ActivationReaction);
00285 
00286         MichaelisMentenDephosphorylationReaction *BRafbyPPtaseDeactivationReaction = new MichaelisMentenDephosphorylationReaction(Raf1PPtase, BRafActive, BRafInactive, k_dBRaf, Km_dBRaf, "BRafbyPPtaseDeactivationReaction");
00287         reactions.push_back(BRafbyPPtaseDeactivationReaction);
00288 }
00289 
00290 CAlternateErkSubnetwork::~CAlternateErkSubnetwork()
00291 {
00292 
00293 }