/* * This code is generated by BioUML FrameWork * for BIOMD0000000033.xml diagram at 2008.03.20 15:04:12 */ import biouml.plugins.simulation.ae.NewtonSolver; import biouml.plugins.simulation.java.JavaBaseModel; import ru.biosoft.math.MathRoutines; public class BIOMD0000000033 extends JavaBaseModel { /* * Write rules to calculate equation parameters */ /* * Write rules to calculate equation parameters excluding internal variables. */ public void __internalRateVarInitFunc_0(double time, double[] x) { rate_AktActivationReaction = cell*(kAkt*x[14]*x[1]/(x[1] + KmAkt)); rate_BRafByRap1ActivationReaction = cell*(kRap1ToBRaf*x[18]*x[3]/(x[3] + KmRap1ToBRaf)); rate_BRafbyPPtaseDeactivationReaction = cell*(kdBRaf*_cell_Raf1PPtase_*x[2]/(x[2] + KmdBRaf)); rate_C3GActivationReaction = cell*(kC3GNGF*x[25]*x[5]/(x[5] + KmC3GNGF)); rate_EGFBindingReaction = cell*krbEGF*x[6]*x[26]; rate_EGFUnbindingReaction = cell*kruEGF*x[24]; rate_ErkActivationReaction = cell*(kpMekCytoplasmic*x[9]*x[8]/(x[8] + KmpMekCytoplasmic)); rate_ErkDeactivationReaction = cell*(kdErk*_cell_PP2AActive_*x[7]/(x[7] + KmdErk)); rate_MekDeactivationReaction = cell*(kdMek*_cell_PP2AActive_*x[9]/(x[9] + KmdMek)); rate_MekbyBRafActivationReaction = cell*(kpBRaf*x[2]*x[10]/(x[10] + KmpBRaf)); rate_MekbyRaf1ActivationReaction = cell*(kpRaf1*x[16]*x[10]/(x[10] + KmpRaf1)); rate_NGFBindingReaction = krbNGF*x[11]*x[27]*cell; rate_NGFUnbindingReaction = kruNGF*x[25]*cell; rate_P90RskActivationReaction = cell*(kpP90Rsk*x[7]*x[13]/(x[13] + KmpP90Rsk)); rate_PI3KbyEGFRActivationReaction = cell*(kPI3K*x[24]*x[15]/(x[15] + KmPI3K)); rate_PI3KbyRasActivationReaction = cell*(kPI3KRas*x[20]*x[15]/(x[15] + KmPI3KRas)); rate_Raf1ByAktDeactivationReaction = cell*(kdRaf1ByAkt*x[0]*x[16]/(x[16] + KmRaf1ByAkt)); rate_Raf1ByRasActivationReaction = cell*(kRasToRaf1*x[20]*x[17]/(x[17] + KmRasToRaf1)); rate_Raf1byPPtaseDeactivationReaction = cell*(kdRaf1*_cell_Raf1PPtase_*x[16]/(x[16] + KmdRaf1)); rate_Rap1ActivationReaction = cell*(kC3G*x[4]*x[19]/(x[19] + KmC3G)); rate_Rap1DeactivationReaction = cell*(kRapGap*_cell_RapGapActive_*x[18]/(x[18] + KmRapGap)); rate_RasActivationReaction = cell*(kSos*x[22]*x[21]/(x[21] + KmSos)); rate_RasDeactivationReaction = cell*(kRasGap*_cell_RasGapActive_*x[20]/(x[20] + KmRasGap)); rate_SosActivationByEGFReaction = cell*(kEGF*x[24]*x[23]/(x[23] + KmEGF)); rate_SosActivationByNGFReaction = cell*(kNGF*x[25]*x[23]/(x[23] + KmNGF)); rate_SosDeactivationReaction = cell*(kdSos*x[12]*x[22]/(x[22] + KmdSos)); } public void Init() { initialValues = getInitialValues(); /* * Initialize variables */ _cell_PP2AActive_ = 120000.0; // initial value of $"cell.PP2AActive" _cell_Raf1PPtase_ = 120000.0; // initial value of $"cell.Raf1PPtase" _cell_RapGapActive_ = 120000.0; // initial value of $"cell.RapGapActive" _cell_RasGapActive_ = 120000.0; // initial value of $"cell.RasGapActive" cell = 1.0; // initial value of $cell KmAkt = 653951.0; // initial value of KmAkt KmC3G = 10965.6; // initial value of KmC3G KmC3GNGF = 12876.2; // initial value of KmC3GNGF KmEGF = 6086070.0; // initial value of KmEGF KmNGF = 2112.66; // initial value of KmNGF KmPI3K = 184912.0; // initial value of KmPI3K KmPI3KRas = 272056.0; // initial value of KmPI3KRas KmRaf1ByAkt = 119355.0; // initial value of KmRaf1ByAkt KmRap1ToBRaf = 1025460.0; // initial value of KmRap1ToBRaf KmRapGap = 295990.0; // initial value of KmRapGap KmRasGap = 1432410.0; // initial value of KmRasGap KmRasToRaf1 = 62464.6; // initial value of KmRasToRaf1 KmSos = 35954.3; // initial value of KmSos KmdBRaf = 1.08795E7; // initial value of KmdBRaf KmdErk = 3496490.0; // initial value of KmdErk KmdMek = 518753.0; // initial value of KmdMek KmdRaf1 = 1061.71; // initial value of KmdRaf1 KmdSos = 896896.0; // initial value of KmdSos KmpBRaf = 157948.0; // initial value of KmpBRaf KmpMekCytoplasmic = 1007340.0; // initial value of KmpMekCytoplasmic KmpP90Rsk = 763523.0; // initial value of KmpP90Rsk KmpRaf1 = 4768350.0; // initial value of KmpRaf1 kAkt = 0.0566279; // initial value of kAkt kC3G = 1.40145; // initial value of kC3G kC3GNGF = 146.912; // initial value of kC3GNGF kEGF = 694.731; // initial value of kEGF kNGF = 389.428; // initial value of kNGF kPI3K = 10.6737; // initial value of kPI3K kPI3KRas = 0.0771067; // initial value of kPI3KRas kRap1ToBRaf = 2.20995; // initial value of kRap1ToBRaf kRapGap = 27.265; // initial value of kRapGap kRasGap = 1509.36; // initial value of kRasGap kRasToRaf1 = 0.884096; // initial value of kRasToRaf1 kSos = 32.344; // initial value of kSos kdBRaf = 441.287; // initial value of kdBRaf kdErk = 8.8912; // initial value of kdErk kdMek = 2.83243; // initial value of kdMek kdRaf1 = 0.126329; // initial value of kdRaf1 kdRaf1ByAkt = 15.1212; // initial value of kdRaf1ByAkt kdSos = 1611.97; // initial value of kdSos kpBRaf = 125.089; // initial value of kpBRaf kpMekCytoplasmic = 9.85367; // initial value of kpMekCytoplasmic kpP90Rsk = 0.0213697; // initial value of kpP90Rsk kpRaf1 = 185.759; // initial value of kpRaf1 krbEGF = 2.18503E-5; // initial value of krbEGF krbNGF = 1.38209E-7; // initial value of krbNGF kruEGF = 0.0121008; // initial value of kruEGF kruNGF = 0.00723811; // initial value of kruNGF } /* * Model variables initial values */ protected double _cell_PP2AActive_; protected double _cell_Raf1PPtase_; protected double _cell_RapGapActive_; protected double _cell_RasGapActive_; protected double rate_AktActivationReaction; protected double rate_BRafByRap1ActivationReaction; protected double rate_BRafbyPPtaseDeactivationReaction; protected double rate_C3GActivationReaction; protected double rate_EGFBindingReaction; protected double rate_EGFUnbindingReaction; protected double rate_ErkActivationReaction; protected double rate_ErkDeactivationReaction; protected double rate_MekDeactivationReaction; protected double rate_MekbyBRafActivationReaction; protected double rate_MekbyRaf1ActivationReaction; protected double rate_NGFBindingReaction; protected double rate_NGFUnbindingReaction; protected double rate_P90RskActivationReaction; protected double rate_PI3KbyEGFRActivationReaction; protected double rate_PI3KbyRasActivationReaction; protected double rate_Raf1ByAktDeactivationReaction; protected double rate_Raf1ByRasActivationReaction; protected double rate_Raf1byPPtaseDeactivationReaction; protected double rate_Rap1ActivationReaction; protected double rate_Rap1DeactivationReaction; protected double rate_RasActivationReaction; protected double rate_RasDeactivationReaction; protected double rate_SosActivationByEGFReaction; protected double rate_SosActivationByNGFReaction; protected double rate_SosDeactivationReaction; protected double cell; protected double KmAkt; protected double KmC3G; protected double KmC3GNGF; protected double KmEGF; protected double KmNGF; protected double KmPI3K; protected double KmPI3KRas; protected double KmRaf1ByAkt; protected double KmRap1ToBRaf; protected double KmRapGap; protected double KmRasGap; protected double KmRasToRaf1; protected double KmSos; protected double KmdBRaf; protected double KmdErk; protected double KmdMek; protected double KmdRaf1; protected double KmdSos; protected double KmpBRaf; protected double KmpMekCytoplasmic; protected double KmpP90Rsk; protected double KmpRaf1; protected double kAkt; protected double kC3G; protected double kC3GNGF; protected double kEGF; protected double kNGF; protected double kPI3K; protected double kPI3KRas; protected double kRap1ToBRaf; protected double kRapGap; protected double kRasGap; protected double kRasToRaf1; protected double kSos; protected double kdBRaf; protected double kdErk; protected double kdMek; protected double kdRaf1; protected double kdRaf1ByAkt; protected double kdSos; protected double kpBRaf; protected double kpMekCytoplasmic; protected double kpP90Rsk; protected double kpRaf1; protected double krbEGF; protected double krbNGF; protected double kruEGF; protected double kruNGF; public double[] extendResult(double time,double [] x) { this.time = time; double[] y = new double[28]; y[0] = x[0]; y[1] = x[1]; y[2] = x[2]; y[3] = x[3]; y[4] = x[4]; y[5] = x[5]; y[6] = x[6]; y[7] = x[7]; y[8] = x[8]; y[9] = x[9]; y[10] = x[10]; y[11] = x[11]; y[12] = x[12]; y[13] = x[13]; y[14] = x[14]; y[15] = x[15]; y[16] = x[16]; y[17] = x[17]; y[18] = x[18]; y[19] = x[19]; y[20] = x[20]; y[21] = x[21]; y[22] = x[22]; y[23] = x[23]; y[24] = x[24]; y[25] = x[25]; y[26] = x[26]; y[27] = x[27]; return y; } public double[] getInitialValues() { double [] x = new double[28]; this.time = 0.0; x[0] = 0.0; // - $"cell.AktActive" x[1] = 120000.0; // - $"cell.AktInactive" x[2] = 0.0; // - $"cell.BRafActive" x[3] = 120000.0; // - $"cell.BRafInactive" x[4] = 0.0; // - $"cell.C3GActive" x[5] = 120000.0; // - $"cell.C3GInactive" x[6] = 1.0002E7; // - $"cell.EGF" x[7] = 0.0; // - $"cell.ErkActive" x[8] = 600000.0; // - $"cell.ErkInactive" x[9] = 0.0; // - $"cell.MekActive" x[10] = 600000.0; // - $"cell.MekInactive" x[11] = 456000.0; // - $"cell.NGF" x[12] = 0.0; // - $"cell.P90RskActive" x[13] = 120000.0; // - $"cell.P90RskInactive" x[14] = 0.0; // - $"cell.PI3KActive" x[15] = 120000.0; // - $"cell.PI3KInactive" x[16] = 0.0; // - $"cell.Raf1Active" x[17] = 120000.0; // - $"cell.Raf1Inactive" x[18] = 0.0; // - $"cell.Rap1Active" x[19] = 120000.0; // - $"cell.Rap1Inactive" x[20] = 0.0; // - $"cell.RasActive" x[21] = 120000.0; // - $"cell.RasInactive" x[22] = 0.0; // - $"cell.SosActive" x[23] = 120000.0; // - $"cell.SosInactive" x[24] = 0.0; // - $"cell.boundEGFReceptor" x[25] = 0.0; // - $"cell.boundNGFReceptor" x[26] = 80000.0; // - $"cell.freeEGFReceptor" x[27] = 10000.0; // - $"cell.freeNGFReceptor" __internalRateVarInitFunc_0(time, x); return x; } /* * code for algebraic rules calculations */ /* * end of code for algebraic rules calculations */ protected void calculateRates(double time, double[] x) { __internalRateVarInitFunc_0(time, x); } /* * calculate dy/dt for 'BIOMD0000000033.xml' model */ public void __internalDyDt_0(double time, double [] x, double[] result) { result[0] = +rate_AktActivationReaction; result[1] = -rate_AktActivationReaction; result[2] = +rate_BRafByRap1ActivationReaction-rate_BRafbyPPtaseDeactivationReaction; result[3] = -rate_BRafByRap1ActivationReaction+rate_BRafbyPPtaseDeactivationReaction; result[4] = +rate_C3GActivationReaction; result[5] = -rate_C3GActivationReaction; result[6] = -rate_EGFBindingReaction+rate_EGFUnbindingReaction; result[7] = +rate_ErkActivationReaction-rate_ErkDeactivationReaction; result[8] = -rate_ErkActivationReaction+rate_ErkDeactivationReaction; result[9] = -rate_MekDeactivationReaction+rate_MekbyBRafActivationReaction+rate_MekbyRaf1ActivationReaction; result[10] = +rate_MekDeactivationReaction-rate_MekbyBRafActivationReaction-rate_MekbyRaf1ActivationReaction; result[11] = -rate_NGFBindingReaction+rate_NGFUnbindingReaction; result[12] = +rate_P90RskActivationReaction; result[13] = -rate_P90RskActivationReaction; result[14] = +rate_PI3KbyEGFRActivationReaction+rate_PI3KbyRasActivationReaction; result[15] = -rate_PI3KbyEGFRActivationReaction-rate_PI3KbyRasActivationReaction; result[16] = -rate_Raf1ByAktDeactivationReaction+rate_Raf1ByRasActivationReaction-rate_Raf1byPPtaseDeactivationReaction; result[17] = +rate_Raf1ByAktDeactivationReaction-rate_Raf1ByRasActivationReaction+rate_Raf1byPPtaseDeactivationReaction; result[18] = +rate_Rap1ActivationReaction-rate_Rap1DeactivationReaction; result[19] = -rate_Rap1ActivationReaction+rate_Rap1DeactivationReaction; result[20] = +rate_RasActivationReaction-rate_RasDeactivationReaction; result[21] = -rate_RasActivationReaction+rate_RasDeactivationReaction; result[22] = +rate_SosActivationByEGFReaction+rate_SosActivationByNGFReaction-rate_SosDeactivationReaction; result[23] = -rate_SosActivationByEGFReaction-rate_SosActivationByNGFReaction+rate_SosDeactivationReaction; result[24] = +rate_EGFBindingReaction-rate_EGFUnbindingReaction; result[25] = +rate_NGFBindingReaction-rate_NGFUnbindingReaction; result[26] = -rate_EGFBindingReaction+rate_EGFUnbindingReaction; result[27] = -rate_NGFBindingReaction+rate_NGFUnbindingReaction; } protected double [] calculateResult(double time, double[] x) { double[] result = new double[28]; __internalDyDt_0(time, x, result); return result; } public double[] dy_dt(double time, double[] x) { this.time = time; calculateRates( time,x ); return calculateResult( time,x ); } } // class ...