#generic model for budding yeast with Wee1 and Cdc25, mass can be saturating
#characteristics for budding yeast include
#CycA=Clb5, CycE=Cln2, CycD=Cln3, CKI=Sic1+Cdc6, 
#No association of CycE and CKI
#kasse=0,kdisse=0, TriE=0
#dMass/dt=mu*Mass*(1-Mass/MaxMass)

#Functions 

BB(A1,A2,A3,A4)=A2-A1+A3*A2+A4*A1
GK(A1,A2,A3,A4)=2.0*A4*A1/(BB(A1,A2,A3,A4)+(BB(A1,A2,A3,A4)^2.0-4.0*(A2-A1)*A4*A1)^.5)
Mass_u5f_(k1)=k1
Mass_0001(k1,S1)=k1*S1
Mass_0002(k1,S1,S2)=k1*S1*S2
Michaelis(M1,J1,k1,S1)=k1*S1*M1/(J1+S1)

#Compartment Equations


#Species 

preMPF=pB+pBCKI
aux preMPF=preMPF

TriB=BCKI+pBCKI
aux TriB=TriB

CycBT=CycB+pB+BCKI+pBCKI
aux CycBT=CycBT

CycAT=CycA+TriA
aux CycAT=CycAT

CycET=CycE+TriE
aux CycET=CycET

CycD=CycD0*Mass
aux CycD=CycD

CKIT=CKI+BCKI+pBCKI+TriA+TriE
aux CKIT=CKIT

Cdc20T=Cdc20i+Cdc20A
aux Cdc20T=Cdc20T

Cdc14=Cdc20A

Wee1=GK(kawee_p+kawee_pp*Cdc14,kiwee_p+kiwee_pp*CycB,Jawee,Jiwee)
aux Wee1=Wee1

Vwee=kwee_p+kwee_pp*Wee1

Cdc25=GK(ka25_p+ka25_pp*CycB,ki25_p+ki25_pp*Cdc14,Ja25,Ji25)
aux Cdc25=Cdc25

V25=k25_p+k25_pp*Cdc25

TFB=GK(kafb*CycB,kifb,Jafb,Jifb)
aux TFB=TFB

Vatf=katf_p+katfa_pp*CycA+katfe_pp*CycE+katfd_pp*CycD
Vitf=kitf_p+kitfa_pp*CycA+kitfb_pp*CycB
TFE=GK(Vatf,Vitf,Jatf,Jitf)
aux TFE=TFE

TFI=GK(kafi*Cdc14,kifi_p+kifib_pp*CycB,Jafi,Jifi)
aux TFI=TFI

Vsb=(ksb_p+ksb_pp*TFB)*Mass
Vsa=(ksa_p+ksa_pp*TFE)*Mass
Vse=(kse_p+kse_pp*TFE)*Mass
Vah1=kah1_p+kah1_pp*Cdc14
Vih1=kih1_p+kih1a_pp*CycA+kih1b_pp*CycB+kih1e_pp*CycE+kih1d_pp*CycD
Vdb=kdb_p+kdbh_pp*Cdh1+kdbc_pp*Cdc20A
Vda=kda_p+(kda_pp+kda_ppp)*Cdc20A+kda_ppp*Cdc20i
Vde=kde_p+kdee_pp*CycE+kdea_pp*CycA+kdeb_pp*CycB
Vsi=ksi_p+ksi_pp*TFI
Vdi=(kdi_p+kdia_pp*CycA+kdib_pp*CycB+kdie_pp*CycE+kdid_pp*CycD)/(1.0+k14di*Cdc14)

#Parameter Equations


#Velocities and Dependent Variables

APC=(-(APCP-APCT)/1)
Cdh1i=(-(Cdh1-Cdh1T)/1)

#Independent Species 

dCycA/dt= - (kassa*CKI*CycA) + (kdissa*TriA) + (Vdi*TriA) + (Vsa) - (Vda*CycA)

dCycB/dt=(Vsb) - (Vdb*CycB) + (V25*pB) - (Vwee*CycB) - (kassb*CycB*CKI) + (kdissb*BCKI) + (Vdi*BCKI)

dCycE/dt= - (kasse*CKI*CycE) + (kdisse*TriE) + (Vdi*TriE) + (Vse) - (Vde*CycE)

dAPCP/dt=(Michaelis(CycB,Jaie,kaie,APC)) - (Michaelis(1.0,Jiie,kiie,APCP))

dBCKI/dt=(kassb*CycB*CKI) - (kdissb*BCKI) + (V25*pBCKI) - (Vwee*BCKI) - (Vdb*BCKI) - (Vdi*BCKI)

dCdc20A/dt=(Michaelis(APCP,Ja20,ka20,Cdc20i)) - (Michaelis(1.0,Ji20,ki20,Cdc20A)) - (kd20*Cdc20A)

dCdc20i/dt=(ks20_p+ks20_pp*CycB^n20/(J20^n20+CycB^n20)) - (kd20*Cdc20i) - (Michaelis(APCP,Ja20,ka20,Cdc20i)) + (Michaelis(1.0,Ji20,ki20,Cdc20A))

dCdh1/dt=(Michaelis(Vah1,Jah1,1.0,Cdh1i)) - (Michaelis(Vih1,Jih1,1.0,Cdh1))

dCKI/dt= - (kassb*CycB*CKI) + (kdissb*BCKI) - (kassb*pB*CKI) + (kdissb*pBCKI) + (Vdb*BCKI) + (Vdb*pBCKI) + (Vsi) - (Vdi*CKI) - (kassa*CKI*CycA) + (kdissa*TriA) + (Vda*TriA) - (kasse*CKI*CycE)  \
+ (kdisse*TriE) + (Vde*TriE)

dMass/dt=mu*Mass*(1-Mass/MaxMass)

dpB/dt= - (V25*pB) + (Vwee*CycB) - (Vdb*pB) - (kassb*pB*CKI) + (kdissb*pBCKI) + (Vdi*pBCKI)

dpBCKI/dt=(kassb*pB*CKI) - (kdissb*pBCKI) - (V25*pBCKI) + (Vwee*BCKI) - (Vdb*pBCKI) - (Vdi*pBCKI)

dTriA/dt=(kassa*CKI*CycA) - (kdissa*TriA) - (Vdi*TriA) - (Vda*TriA)

dTriE/dt=(kasse*CKI*CycE) - (kdisse*TriE) - (Vdi*TriE) - (Vde*TriE)

#Globals 

global -1 {CycB-KEZ-0.0} {Mass=0.5*Mass }

init CycA=0.09450308233499527  
init CycB=0.1903585940599442  
init CycE=0.2092024385929108  
init APCP=0.07591402530670166  
init BCKI=0.679449200630188  
init Cdc20A=0.3572723865509033  
init Cdc20i=0.7702387571334839  
init Cdh1=0.7189393639564514  
init CKI=0.02882070094347  
init Mass=1.338267803192139  
init pB=0.01234426256269217  
init pBCKI=0.04795938357710838  
init TriA=0.3492224216461182  
init TriE=0.0

#CycD0=Cln3+Bck2
param CycD0=0.108

#CycE=Cln2
param kse_p=0.0
param kse_pp=0.15
param kde_p=0.12
param kdea_pp=0.0
param kdeb_pp=0.0
param kdee_pp=0.0
param kasse=0.0
param kdisse=0.0

#TFE=SBF
param katf_p=0.0
param katfa_pp=1.5
param katfd_pp=3.0
param katfe_pp=0.38
param kitf_p=0.75
param kitfa_pp=0.0
param kitfb_pp=8.0
param Jatf=0.01
param Jitf=0.01

#CycB=Clb2
param ksb_p=0.0040
param ksb_pp=0.04
param kdb_p=0.0030
param kdbh_pp=0.4
param kdbc_pp=0.15
param kassb=60.0
param kdissb=0.05
param kwee_p=0.02
param kwee_pp=0.2
param k25_p=0.01
param k25_pp=5

#TFB=MCM1
param kafb=1.0
param kifb=0.15
param Jafb=0.1
param Jifb=0.1

#CycA=Clb5
param ksa_p=0.0015
param ksa_pp=0.01
param kda_p=0.01
param kda_pp=0.16
param kda_ppp=0.0
param kassa=50.0
param kdissa=0.06

#CKI=Sic1+Cdc6
param ksi_p=0.018
param ksi_pp=0.18
param kdi_p=0.002
param kdia_pp=0.1
param kdib_pp=0.8
param kdid_pp=0.1
param kdie_pp=0.12
param k14di=12.0

#TFI=Swi5
param kafi=6.0
param kifi_p=0.0080
param kifib_pp=0.05
param Jafi=1.0
param Jifi=2.0

#APC activation
param kaie=0.1
param kiie=0.15
param Jaie=0.1
param Jiie=0.1

#Cdc20
param ks20_p=0.0010
param ks20_pp=1.0
param n20=1.0
param J20=10.0
param kd20=0.05
param ka20=1.0
param ki20=0.16
param Ja20=1.0
param Ji20=1.0

#Cdh1
param kah1_p=0.02
param kah1_pp=0.8
param kih1_p=0.0010
param kih1a_pp=0.35
param kih1b_pp=0.1
param kih1d_pp=0.005
param kih1e_pp=0.06
param Jah1=0.03
param Jih1=0.03

#Wee1-Cdc25
param kawee_p=0.3
param kawee_pp=0.0
param kiwee_p=0
param kiwee_pp=1
param Jawee=0.05
param Jiwee=0.05
param ka25_p=0
param ka25_pp=1
param ki25_p=0.3
param ki25_pp=0
param Ja25=0.1
param Ji25=0.1

param APCT=1.0
param Cdh1T=1.0
param cell=1
param KEZ=0.2
param mu=0.005776
param MaxMass=10000

@ Maxstore=100000, bound=2000, dt=0.1
@ Meth=Stiff, total=500, xplot=t, xlo=0, xhi=500, ylo=0, yhi=4
@ nplot=6, yp1=Mass, yp2=Cdh1, yp3=CKIT, yp4=CycA, yp5=CycE, yp6=CycB 

done