from pysb import *

from pysb.macros import catalyze, degrade, equilibrate, bind, bind_table, synthesize

# instantiate a model

Model()

#Declare Monomers

Monomer('Cb',['b', 'S'], {'S':['i', 'a']})

Monomer('Cdk1',['b', 'c', 'S'], {'S':['i', 'a']})

Monomer('p27_p21',['b', 'S'], {'S':['u', 'p']})

Monomer('Wee1',['b', 'S'], {'S':['a', 'i']})

Monomer('CDC25', ['b', 'S'], {'S':['a', 'i']})

Monomer('CDC20', ['b', 'S'], {'S':['a', 'i']})

Monomer('Cdh1', ['b', 'S'], {'S':['a', 'i']})

#Declare Parameters

#Parameter for Synthesis of Cyclin B

Parameter('kSCb', 8.0e-04) #FILL IN VALUE- THIS VALUE IS NOT IN IWAMOTO PAPER

#Parameter for Degradation of Cyclin B

Parameter('kDCb', 5.0e-04) #FILL IN VALUE- THIS VALUE IS NOT IN IWAMOTO PAPER

#Cyclin B/Cdk1 binding parameters:

Parameter('kcdk1f',1.0e-03)

Parameter('kcdk1r', 2.0e-04) #FILL IN VALUES- THESE VALUES ARE NOT IN IWAMOTO PAPER

#CyclinB/Cdk1 Complex Equilibrate Parameters:

Parameter('kfcbcdk', 1.9e-02) #FILL IN VALUE- THIS VALUE IS NOT IN IWAMOTO PAPER

Parameter('krcbcdk', 5.0e-04) #FILL IN VALUE- THIS VALUE IS NOT IN IWAMOTO PAPER

#Cyclin B/Cdk1/p27_p21 binding parameters:

Parameter('kfcp27_p21', 1.5e-03) #FILL IN VALUE- THIS VALUE IS NOT IN IWAMOTO PAPER

Parameter('krcp27_p21', 1.75e-04) #FILL IN VALUE- THIS VALUE IS NOT IN IWAMOTO PAPER

#Paramerers for CDC25 equilibration:

Parameter('kfCDC25', 5.0e-08) #THESE PARAMETERS ARE NOT CORRECT- ESTIMATED FOR NOW. CDC25 IS NOT IN IWAMOTO PAPER

Parameter('krCDC25', 2.5e-03) #THESE PARAMETERS ARE NOT CORRECT- ESTIMATED FOR NOW. CDC25 IS NOT IN IWAMOTO PAPER

#Parameters for CDC20 equilibration:

Parameter('kfCDC20', 5.0e-08) #THESE PARAMETERS ARE NOT CORRECT- ESTIMATED FOR NOW. CDC20 IS NOT IN IWAMOTO PAPER

Parameter('krCDC20', 2.5e-03) #THESE PARAMETERS ARE NOT CORRECT- ESTIMATED FOR NOW. CDC20 IS NOT IN IWAMOTO PAPER

#Parameters for Wee1 equilibration:

Parameter('kfWee1', 5.0e-08) #THESE PARAMETERS ARE NOT CORRECT- ESTIMATED FOR NOW. Check Iwamoto

Parameter('krWee1', 2.5e-03) #THESE PARAMETERS ARE NOT CORRECT- ESTIMATED FOR NOW. Check Iwamoto

#Observables

#Observable('obsCdh1i', Cdh1(b=None, S='i'))

#Observable('obsCdh1a', Cdh1(b=None, S='a'))

Observable('obsCbi', Cb(b=None, S='i'))

Observable('obsCba', Cb(b=None, S='a'))

Observable('obsCb_Cdk1i', Cb(b=1, S='a') % Cdk1(b=1, S ='i'))

Observable('obsCb_Cdk1a', Cb(b=1, S='a') % Cdk1(b=1, S ='a'))

Observable('obsCb_Cdk1a_p27', Cb(b=1, S='i') % Cdk1(b=1, c=2, S ='i') % p27_p21(b=2, S='u'))

Observable('obsp27_p21u', p27_p21(b=None, S='u'))

Observable('obsp27_p21p', p27_p21(b=None, S='p'))

Observable('obsWee1i', Wee1(b=None, S='i'))

Observable('obsWee1a', Wee1(b=None, S='a'))

Observable('obsCDC25i', CDC25(b=None, S='i'))

Observable('obsCDC25a', CDC25(b=None, S='a'))

Observable('obsCDC20i', CDC25(b=None, S='i'))

Observable('obsCDC20a', CDC25(b=None, S='a'))

Observable('obsCdk1i', Cdk1(b=None, c= None, S='i'))

Observable('obsCdk1a', Cdk1(b=None, c= None, S='a'))

#Initial Conditions

Parameter('Cb_0', 4.0e-05) #VALUE NOT CORRECT

Initial(Cb(b=None, S='a'), Cb_0)

Parameter('Cdk1_0', 1.35e01) #VALUE NOT CORRECT

Initial(Cdk1(b=None, c=None, S='i'),Cdk1_0)

Parameter('Cb_Cdk1i_0', 4.0e-04) #VALUE NOT CORRECT

Initial(Cb(b=1, S='a') % Cdk1(b=1, c=None, S='i'), Cb_Cdk1i_0)

Parameter('Cb_Cdk1a_0', 1.0e-04) ##VALUE NOT CORRECT

Initial(Cb(b=1, S='a') % Cdk1(b=1, c=None, S='a'), Cb_Cdk1a_0)

Parameter('p27_21_0', 1.0e01) #Y10 in Iwamoto

Initial(p27_p21(b=None, S='u'),p27_21_0)

Parameter('Cb_Cdk1_p27_p21_0', 1.0e-04) #VALUE NOT CORRECT

Initial(Cb(b=1, S='a') % Cdk1(b=1, c=2, S='a') % p27_p21(b=2, S='u'), Cb_Cdk1_p27_p21_0)

Parameter('CDC25_0', 1.0e01) #THIS PARAMETER IS NOT CORRECT- ESTIMATED FOR NOW- NOT IN IWAMOTO PAPER

Initial(CDC25(b=None, S='i'), CDC25_0)

#Declare Rules

#Cyclin B Synthesis and Degradation

synthesize(Cb(b=None, S = 'a'), kSCb)

degrade(Cb(b=None, S='a'),kDCb)

#Cyclin B binds to Cdk1

Rule('Cb_Cdk1_bind',Cb(b=None, S='a') + Cdk1(b=None, c=None, S='i') <> Cb(b=1, S='a') % Cdk1(b=1, c=None, S ='i'), *[kcdk1f, kcdk1r])

#The Cb/Cdk1 complex equilibrates from inactive to active

equilibrate(Cb(b=1, S='a') % Cdk1(b=1, c=None, S='i'),Cb(b=1, S='a') % Cdk1(b=1, c=None, S='a'),[kfcbcdk,krcbcdk])

#The Cb/Cdk1 complex binds to p27_p21 - this complex is inactive

Rule ('Cb_Cdk1_p27_p21_bind',p27_p21(b=None, S='u') + Cb(b=1, S='a') % Cdk1(b=1, c=None, S='a') <> Cb(b=1, S='i') % Cdk1(b=1, c=2, S ='i') % p27_p21(b=2, S='u') , *[kfcp27_p21, krcp27_p21])

#Equilibrate CDC25

equilibrate(CDC25(b=None,S='i'),CDC25(b=None, S='a'),[kfCDC25, krCDC25])

#Equilibrate CDC20

equilibrate(CDC20(b=None,S='i'),CDC20(b=None, S='a'),[kfCDC20, krCDC20])

#Equilibrate Wee1

equilibrate(Wee1(b=None,S='i'),Wee1(b=None, S='a'),[kfWee1, krWee1])

##JUST NEED TO SHOW THE EFFECTS OF MONOMERS AND COMPLEXES ON OTHER MONOMERS AND COMPLEXES NOW