begin parameters #NA 6.02e23 # Avogadro's number (molecues/mol) #f 0.1 # Fraction of the cell to simulate #Vo f*1.0e-10 # Extracellular volume=1/cell_density (L) #V f*3.0e-12 # Cytoplasmic volume (L) NA 1 f 1 Vo 1 V 1 k1 1 V21 .005 V22 .25 k3 .005/(NA*V) V251 .017/(NA*V) V252 .17/(NA*V) Vwee1 .01/(NA*V) Vwee2 1/(NA*V) ka .02 Ka .1 kb .1 Kb 1 kc .13 Kc .01 kd .13 Kd 1 ke .02 Ke .1 kf .1 Kf 1 kg .02 Kg .01 kh .15 Kh .01 TotCdk 100*NA*V*f TotCdc25 1*NA*V*f TotWee1 1*NA*V*f TotIE 1*NA*V*f TotAPC 1*NA*V*f PPase 1*NA*V*f AA 1*NA*V*f init_cyclin 0 init_MPF 0 init_preMPF 0 init_cdc25p 0 init_wee1p 0 init_iep 0 init_APCon 0 zero 0 end parameters begin molecule types I() Cyclin(deg~y~n) APC(c~OFF~ON) Cdk() MPF(cyclin,cdk~U~1P~2P) Wee1(c~P~U) Cdc25(c~P~U) PPase() IE(c~P~U) end molecule types begin seed species Species0: Cyclin(deg~n) init_cyclin Species1: MPF(cyclin,cdk~1P) init_MPF Species2: MPF(cyclin,cdk~2P) init_preMPF Species3: Cdc25(c~P) init_cdc25p Species4: Cdc25(c~U) TotCdc25-init_cdc25p Species5: PPase() PPase Species6: Wee1(c~P) init_wee1p Species7: Wee1(c~U) TotWee1-init_wee1p Species8: IE(c~P) init_iep Species9: IE(c~U) TotIE-init_iep Species10: APC(c~ON) init_APCon Species11: APC(c~OFF) TotAPC-init_APCon Species12: I() AA Species13: Cdk() TotCdk end seed species begin reaction rules Rule0: I()->I()+Cyclin(deg~n) k1 Rule1: Cyclin(deg~n)+APC(c~OFF)->Cyclin(deg~y)+APC(c~OFF) V21 Rule2: Cyclin(deg~n)+APC(c~ON)->Cyclin(deg~y)+APC(c~ON) V22 Rule3: Cyclin(deg~n)+Cdk()->MPF(cyclin,cdk~1P) k3 Rule4: MPF(cyclin)+APC(c~OFF)->Cyclin(deg~y)+APC(c~OFF)+Cdk() V21 Rule5: MPF(cyclin)+APC(c~ON)->Cyclin(deg~y)+APC(c~ON)+Cdk() V22 Rule6: MPF(cyclin,cdk~1P)+Wee1(c~P)->MPF(cyclin,cdk~2P)+Wee1(c~P) Vwee1 Rule7: MPF(cyclin,cdk~1P)+Wee1(c~U)->MPF(cyclin,cdk~2P)+Wee1(c~U) Vwee2 Rule8: MPF(cyclin,cdk~2P)+Cdc25(c~P)->MPF(cyclin,cdk~1P)+Cdc25(c~P) V252 Rule9: MPF(cyclin,cdk~2P)+Cdc25(c~U)->MPF(cyclin,cdk~1P)+Cdc25(c~U) V251 Rule10: Cdc25(c~U)+MPF(cyclin,cdk~1P)->Cdc25(c~P)+MPF(cyclin,cdk~1P) Sat(ka,Ka) Rule11: Cdc25(c~P)+PPase()->Cdc25(c~U)+PPase() Sat(kb,Kb) Rule12: Wee1(c~U)+MPF(cyclin,cdk~1P)->Wee1(c~P)+MPF(cyclin,cdk~1P) Sat(ke,Ke) Rule13: Wee1(c~P)+PPase()->Wee1(c~U)+PPase() Sat(kf,Kf) Rule14: IE(c~U)+MPF(cyclin,cdk~1P)->IE(c~P)+MPF(cyclin,cdk~1P) Sat(kg,Kg) Rule15: IE(c~P)+PPase()->IE(c~U)+PPase() Sat(kh,Kh) Rule16: APC(c~OFF)+IE(c~P)->APC(c~ON)+IE(c~P) Sat(kc,Kc) Rule17: APC(c~ON)+PPase()->APC(c~OFF)+PPase() Sat(kd,Kd) end reaction rules begin observables Molecules Tot_Cyclin Cyclin(deg~n) MPF(cyclin,cdk~1P) MPF(cyclin,cdk~2P) Molecules Cyclin Cyclin(deg~n) Molecules Wee1P Wee1(c~P) Molecules Cdc25P Cdc25(c~P) Molecules IEP IE(c~P) Molecules APCon APC(c~ON) Molecules MPF MPF(cyclin,cdk~1P) Molecules preMPF MPF(cyclin,cdk~2P) end observables #generate_network({overwrite=>1,check_iso=>1,max_iter=>25,}); #simulate_ode({t_end=>500,n_steps=>250,atol=>1e-12,rtol=>1e-12,sparse=>0}); generate_network({overwrite=>1}); simulate_ode({t_end=>500,n_steps=>250,atol=>1e-12,rtol=>1e-12});