#model"HET_full"; // Effects of Dimerization in Toggle Switch // Cheol-Min Ghim, cmghim@llnl.gov // 01-17-2009 /*******************************************************************/ // Initial Copy Numbers of Elements /*******************************************************************/ A = 5; // A-protein B = 4; // B-protein RP = 30; // RNA polymerase, boundary species MRa = 16; // A mRNA MRb = 14; // B mRNA AB = 2; // AB-complex /*******************************************************************/ DA0 = 0; // bare A-DNA DB0 = 0; // bare B-DNA DBa = 1; // A2 bound to O_B DBaa = 0; // A2 bound to O_B DAb = 1; // B2 bound to O_A DAbb = 0; // B2 bound to O_A DAR = 0; // RNAp bound to Promoter A DBR = 0; // RNAp bound to Promoter B DBaR = 0; // RNAp bound to DBa DAbR = 0; // RNAp bound to DAb DAbbR = 0; // RNAp bound to Promoter A DBaaR = 0; // RNAp bound to Promoter B /*******************************************************************/ EA = 4; EB = 4; /******************************************************************** * List of Kinetic Parameters ********************************************************************/ // Cooperativity factor r = 5; // TF binding cooperativity s = 0.1; // leakage // Rate parameters kf1 = 0.1; // K1 = 10 nM kr1 = 1.0; // kf2 = 0.01; // K2 = 20 nM kr2 = 0.2; // kf3 = 0.01; // RNAp-promoter kr3 = 0.4; // K3 = 90 nM //kr3 = 0.9; // K3 = 90 nM kf4 = kf2*r; // TF cooperativity K2/K4=r^2 kr4 = kr2/r; // Isomerization of RNAp-Promoter closed to open complex // reinterpreted from Hawley & McClure (1982) clear = 0.5; // isomerization & clearance kf5 = kf3*s; // promoter leakage K3/K5=s^2 kr5 = (kr3+clear)/s-clear; /*******************************************************************/ alpha_m = 0.0156; // elongation speed ~40 nt/sec, ~1 kbp/gene alpha_p = 0.0156; // ~15 aa/sec gamma_m = 0.0039; // ~(ln 2)/(3 min) gamma_p = 0.05; /*******************************************************************/ // Reversible Binding-Unbinding Reactions (Fast) /*******************************************************************/ AB_bind, A + B -> AB, kf1; AB_unbind, AB -> A + B, kr1; // TF binding A_Op_bind, A + DB0 -> DBa, kf2; A_Op_unbind, DBa -> A + DB0, kr2; B_Op_bind, B + DA0 -> DAb, kf2; B_Op_unbind, DAb -> B + DA0, kr2; A_OpA_bind, A + DBa -> DBaa, kf4; A_OpA_unbind, DBaa -> A + DBa, kr4; B_OpB_bind, B + DAb -> DAbb, kf4; B_OpB_unbind, DAbb -> B + DAb, kr4; // RNAp binding RNAp_ProA_bind, $RP + DA0 -> DAR, kf3; RNAp_ProA_unbind, DAR -> DA0, kr3; RNAp_ProB_bind, $RP + DB0 -> DBR, kf3; RNAp_ProB_unbind, DBR -> DB0, kr3; // Leakage 1 RNAp_Leak1A_bind, $RP + DAb -> DAbR, kf5; RNAp_Leak1A_unbind, DAbR -> DAb, kr5; RNAp_Leak1B_bind, $RP + DBa -> DBaR, kf5; RNAp_Leak1B_unbind, DBaR -> DBa, kr5; // Leakage 2 RNAp_Leak2A_bind, $RP + DAbb -> DAbbR, kf5; RNAp_Leak2A_unbind, DAbbR -> DAbb, kr5; RNAp_Leak2B_bind, $RP + DBaa -> DBaaR, kf5; RNAp_Leak2B_unbind, DBaaR -> DBaa, kr5; /*******************************************************************/ // Irreversible Reactions (Slow) /*******************************************************************/ ProA_clearance0, DAR -> DA0 + EA, clear; ProB_clearance0, DBR -> DB0 + EB, clear; ProA_clearance1, DAbR -> DAb + EA, clear; ProB_clearance1, DBaR -> DBa + EB, clear; ProA_clearance2, DAbbR -> DAbb + EA, clear; ProB_clearance2, DBaaR -> DBaa + EB, clear; TSXa, EA -> MRa, alpha_m; TSXb, EB -> MRb, alpha_m; TSLa, MRa -> MRa + A, alpha_p; TSLb, MRb -> MRb + B, alpha_p; mRNAa_decay, MRa -> , gamma_m; mRNAb_decay, MRb -> , gamma_m; Amonomer_decay, A -> , gamma_p; Bmonomer_decay, B -> , gamma_p; AB_decay, AB -> , gamma_p/10;