Python util.alias_model_components函数代码示例

def erk_nuclear_initial(fra1=True, elk1=False):
    alias_model_components() 
    if elk1 == True:
        Initial(ELK1(b=None, S383='U'), ELK1_0)
    
    if fra1 == True:
        Initial(FRA1(b=None, st='U'), FRA1_0)

def mapk_initial():

    # Initial conditions obtained from Schoeberl et al.
    Parameter('GAP_0', 1.2e4)
    Parameter('SHC_0', 1.01e6)
    # Parameter('SHCPase_0', 1000)
    Parameter('GRB2_0', 5.1e4)
    Parameter('SOS_0', 6.63e4)
    Parameter('RAS_0', 1.14e7)
    Parameter('RAF_0', 4e4)
    Parameter('MEK_0', 2.2e7)
    Parameter('ERK_0', 2.1e7)
    Parameter('PP1_0', 4e4)
    Parameter('PP2_0', 4e4)
    Parameter('PP3_0', 1e7)

    alias_model_components()

    Initial(GAP(bd=None, b=None), GAP_0)
    Initial(SHC(bgap=None, bgrb=None, batp=None, st='U'), SHC_0)
    Initial(GRB2(b=None, bsos=None), GRB2_0)
    Initial(SOS(bgrb=None, bras=None), SOS_0)
    Initial(RAS(bsos=None, braf=None, st='GDP'), RAS_0)
    Initial(RAF(b=None, st='U'), RAF_0)
    Initial(MEK(b=None, st='U'), MEK_0)
    Initial(ERK(b=None, st='U'), ERK_0)
    Initial(PP1(b=None), PP1_0)
    Initial(PP2(b=None), PP2_0)
    Initial(PP3(b=None), PP3_0)

def albeck_11c(do_pore_transport=True):
    """Model incorporating Bax oligomerization.

    Features:
        - Bid activates Bax
        - Active Bax dimerizes; Bax dimers dimerize to form tetramers
        - Bcl2 binds/inhibits Bax monomers, dimers, and tetramers
        - Bax tetramers bind to and transport Smac to the cytosol
    """

    alias_model_components()
    Initial(Bid(state='U', bf=None), Parameter('Bid_0', 4e4))
    Initial(Bax(bf=None, **inactive_monomer), Parameter('Bax_0', 1e5))
    Initial(Bcl2(bf=None), Parameter('Bcl2_0', 2e4))

    # tBid activates Bax
    catalyze(Bid(state='T'), Bax(inactive_monomer), Bax(active_monomer),
             [1e-7, KR, KC])

    # Bax dimerizes/tetramerizes
    Bax_tetramerizes(bax_active_state='A')

    # Bcl2 inhibits Bax, Bax2, and Bax4
    Bcl2_binds_Bax1_Bax2_and_Bax4(bax_active_state='A')

    if do_pore_transport:
        Initial(Smac(state='M', bf=None), Parameter('Smac_0', 1e6))
        Initial(CytoC(state='M', bf=None), Parameter('CytoC_0', 1e6))
        # NOTE change in KF here from previous model!!!!
        pore_transport(Bax(state='A'), 4, Smac(state='M'), Smac(state='C'),
            [[2*KF, KR, 10]])
        pore_transport(Bax(state='A'), 4, CytoC(state='M'), CytoC(state='C'),
            [[KF, KR, 10]])

def erk_autophos():
    # * How does ERK autophosphorylate?
    # Does an already phosphorylated ERK phosphorylate another one?
    Parameter('kp_erk', 1e-8)
    alias_model_components()
    Rule('ERK_autophos', ERK(b=1, Y='u') % ERK(b=1, Y='p') >>\
                        ERK(b=1, Y='p') % ERK(b=1, Y='p'), kp_erk)

def declare_initial_conditions():
    """Declare initial conditions for Bcl-2 family proteins, Cyto c, and Smac.
    """
    #Parameter('Bid_0'   , 4.0e4) # Bid
    Parameter('BclxL_0' , 2.0e4) # cytosolic BclxL
    Parameter('Mcl1_0'  , 2.0e4) # Mitochondrial Mcl1
    Parameter('Bcl2_0'  , 2.0e4) # Mitochondrial Bcl2
    Parameter('Bad_0'   , 1.0e3) # Bad
    Parameter('Noxa_0'  , 1.0e3) # Noxa
    Parameter('CytoC_0' , 5.0e5) # cytochrome c
    Parameter('Smac_0'  , 1.0e5) # Smac
    Parameter('Bax_0'   , 0.8e5) # Bax
    Parameter('Bak_0'   , 0.2e5) # Bak

    alias_model_components()

    #Initial(Bid(bf=None, state='U'), Bid_0)
    Initial(Bad(bf=None, state='C'), Bad_0)
    Initial(Bax(bf=None, s1=None, s2=None, state='C'), Bax_0)
    Initial(Bak(bf=None, s1=None, s2=None, state='M'), Bak_0)
    Initial(Bcl2(bf=None), Bcl2_0)
    Initial(BclxL (bf=None, state='C'), BclxL_0)
    Initial(Mcl1(bf=None, state='M'), Mcl1_0)
    Initial(Noxa(bf=None, state='C'), Noxa_0)
    Initial(CytoC(bf=None, state='M'), CytoC_0)
    Initial(Smac(bf=None, state='M'), Smac_0)

def effectors_bind_anti_apoptotics():
    alias_model_components()
    """Binding of Bax and Bak to Bcl2, BclxL, and Mcl1.

    Affinities of Bak for Bcl-xL and Mcl-1 are taken from Willis et al.

    Preferential affinity of Bax for Bcl-2 and Bcl-xL were taken from Zhai et
    al.  Bax:Bcl2 and Bax:Bcl-xL affinities were given order of magnitude
    estimates of 10nM.

    See comments on units for :py:func:`tBid_binds_all_anti_apoptotics`.

    Willis, S. N., Chen, L., Dewson, G., Wei, A., Naik, E., Fletcher, J. I.,
    Adams, J. M., et al. (2005). Proapoptotic Bak is sequestered by Mcl-1 and
    Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins. Genes &
    Development, 19(11), 1294-1305. `doi:10.1101/gad.1304105`

    Zhai, D., Jin, C., Huang, Z., Satterthwait, A. C., & Reed, J. C. (2008).
    Differential regulation of Bax and Bak by anti-apoptotic Bcl-2 family
    proteins Bcl-B and Mcl-1. The Journal of biological chemistry, 283(15),
    9580-9586.  `doi:10.1074/jbc.M708426200`
    """

    bind_table([[                            Bcl2,  BclxL(state='M'),         Mcl1],
                [Bax(state='A'), 10e-9*N_A*V,       10e-9*N_A*V,         None],
                [Bak(state='A'),        None,       50e-9*N_A*V,  10e-9*N_A*V]],
               'bf', 'bf', kf=1e6/(N_A*V))

def momp_monomers():
    """Declare the monomers used in the Albeck MOMP modules."""

    # == Activators
    # Bid, states: Untruncated, Truncated, truncated and Mitochondrial
    Monomer('Bid', ['bf', 'state'], {'state':['U', 'T', 'M']})

    # == Effectors
    # Bax, states: Cytoplasmic, Mitochondrial, Active
    # sites 's1' and 's2' are used for pore formation
    Monomer('Bax', ['bf', 's1', 's2', 'state'], {'state':['C', 'M', 'A']})

    # == Anti-Apoptotics
    Monomer('Bcl2', ['bf'])

    # == Cytochrome C and Smac
    Monomer('CytoC', ['bf', 'state'], {'state':['M', 'C', 'A']})
    Monomer('Smac', ['bf', 'state'], {'state':['M', 'C', 'A']})

    alias_model_components()

    # == Annotations
    Annotation(Bid, 'http://identifiers.org/uniprot/P55957')
    Annotation(Bax, 'http://identifiers.org/uniprot/Q07812')
    Annotation(Bcl2, 'http://identifiers.org/uniprot/P10415')
    Annotation(CytoC, 'http://identifiers.org/uniprot/P99999')
    Annotation(Smac, 'http://identifiers.org/uniprot/Q9NR28')

def declare_initial_conditions():
    """Declare initial conditions for Bcl-2 family proteins, Cyto c, and Smac.
        Jurkat Cell parameters were used instead of the Hela cells used in Lopez_modules.
        """
    Parameter('Bid_0'   , 12044) # Bid
    Parameter('BclxL_0' , 36132) # cytosolic BclxL (assigned since Bcl-2 in Jurkats is 36132)
    Parameter('Mcl1_0'  , 36132) # Mitochondrial Mcl1 ("")
    Parameter('Bcl2_0'  , 36132) # Mitochondrial Bcl2
    Parameter('Bad_0'   , 1.0e3) # Bad
    Parameter('Noxa_0'  , 1.0e3) # Noxa
    Parameter('CytoC_0' , 48176) # cytochrome c
    Parameter('Smac_0'  , 48176) # Smac
    Parameter('Bax_0'   , 40145) # Bax
    Parameter('Bak_0'   , 0.2e5) # Bak
    
    alias_model_components()
    
    Initial(Bid(bf=None, state='U'), Bid_0)
    Initial(Bad(bf=None, state='C'), Bad_0)
    Initial(Bax(bf=None, s1=None, s2=None, state='C'), Bax_0)
    Initial(Bak(bf=None, s1=None, s2=None, state='M'), Bak_0)
    Initial(Bcl2(bf=None), Bcl2_0)
    Initial(BclxL (bf=None, state='C'), BclxL_0)
    Initial(Mcl1(bf=None, state='M'), Mcl1_0)
    Initial(Noxa(bf=None, state='C'), Noxa_0)
    Initial(CytoC(bf=None, state='M'), CytoC_0)
    Initial(Smac(bf=None, state='M'), Smac_0)

def mkp_dephos_erk_seq():
    """The parameters are based on Table S2 of Markevich et al. 
    But we assume distributive sequential phosphatase mechanism.

    First and second order rate constants are in s^{-1} and nM^{-1}s^{-1}
    respectively.
    """
    Parameter('kf_mkp', 2.9e-3)    # = h_{-6} + h_{-9}
    Parameter('kf_mkp_p', 1e-2)    # = h_{-3} + h_{7}
    Parameter('kf_mkp_pp', 4.5e-2) # = h_1
    Parameter('kr_mkp', 1.4e-1)    # = h_9 which is also used 
                                   #    in the reaction for the original h_6
    Parameter('kr_mkp_p', 1)       # = h_{3} = h_{-4} = h_{-7} = h_{12}
    Parameter('kr_mkp_pp', 1)      # = h_{-1}
    Parameter('kc_mkp', 5e-1)      # = h_5 which is also used
                                   #    in the reaction for the original h_8
    Parameter('kc_mkp_p', 9.2e-2)  # = h_2
    alias_model_components()

    Rule('MKP_bind_ERK_uu', MKP(b=None) + ERK(b=None, T='u', Y='u') <>\
                            MKP(b=1) % ERK(b=1, T='u', Y='u'), kf_mkp, 
                            kr_mkp)
    Rule('MKP_bind_ERK_pY', MKP(b=None) + ERK(b=None, T='u', Y='p') <>\
                            MKP(b=1) % ERK(b=1, T='u', Y='p'), kf_mkp_p,
                            kr_mkp_p)
    Rule('MKP_bind_ERK_pp', MKP(b=None) + ERK(b=None, T='p', Y='p') <>\
                            MKP(b=1) % ERK(b=1, T='p', Y='p'), 
                            kf_mkp_pp, kr_mkp_pp)

    Rule('MKP_dephos_ERK_ppT', MKP(b=1) % ERK(b=1, T='p', Y='p') >>\
                               MKP(b=None) + ERK(b=None, T='u', Y='p'),
                               kc_mkp_p)
    Rule('MKP_dephos_ERK_pY', MKP(b=1) % ERK(b=1, T='u', Y='p') >>\
                              MKP(b=None) + ERK(b=None, T='u', Y='u'),
                              kc_mkp)

def PI3K_monomers():
    """ Declare monomers in the PI3K arm of the pathway, namely, 
        Gab1, ERK, PI3K, Shp2, PIP2, PIP3, PTEN, Shp, AKT, PDK1 Pase9t, and Pase3
        
        A description of sites on the monomers is given below
        ======================================================
        Gab1 sites: 'atp' is a site to bind ATP
                    'grb2' is a site to bind Grb2
                    'shp2' is a site to bind Shp2
                    'erk' is a site to bind ERK
                    'pase' is a site to bind Pase9t
                    'pi3k' is a site to bind PI3K
                    'state' denotes the phoshorylation status of the species, 
                    with 'up' denoting unphosphorylated,'p' donating singly-phoshorylated and 'pp' denoting doubly phoshporylated
       'gab1' are sites on Shp2, Pase9t, and PI3K to bind Gab1 
       'pip' are sites on AKT, Shp, PTEN, PDK1 to bind PIP3
    """

    Monomer('Gab1',['atp', 'grb2', 'shp2', 'state','erk','pase', 'pi3k'], {'state':['up','p', 'pp']})
    Monomer('Shp2',['gab1'])
    Monomer('Pase_9t', ['gab1'])
    Monomer('PI3K', ['gab1', 'pip2', 'ras'])  # 'pip2' and 'ras' are sites on PI3K to bind PIP2 and RAS
    Monomer('PIP2', ['pi3k']) # 'pi3k' is a site on PIP2 to bind PI3K
    Monomer('PIP3', ['akt', 'pdk','bnd']) # 'akt' and 'pdk' are sites on PIP3 to bind AKT and PDK respectively
    Monomer('AKT', ['pip', 'pase', 'raf', 'state'], {'state':['up','p', 'pp']})
    Monomer('PDK1',['pip'])
    Monomer('Shp', ['pip'])
    Monomer('PTEN', ['pip'])
    Monomer('Pase4', ['akt']) # 'akt' is a site on Pase4 to bind AKT

    alias_model_components()

    global receptors
    receptors = [ErbB1, ErbB2, ErbB3, ErbB4]

def bind_Gab1():
    " v688-694 "
    " Gab1 binds receptor dimers via Grb2 only when (1) dimers are in plasma mem (2) Grb2 (no SOS) is directly bound to receptor "
    
    # Initial amount
    # ==============
    Parameter('Gab1_0',94868.3)     # c426
    # Rate constant
    # ==============
    Parameter('k105', 6.67e-05)         # k105
    Parameter('kd105', 0.1)              # kd105
    Parameter('k122_gab', 1.8704e-8)      # k122
    Parameter('kd122_gab', 1.0)          # kd122
    Parameter('kd123_gab', 0.177828)          # kd123

    alias_model_components()
    
    # Initial conditions
    # ==============
    Initial(Gab1(atp=None, grb2=None, shp2=None, erk=None, pase=None, pi3k=None, state='up'), Gab1_0)
    
    # Rules
    # =====
    for erb in receptors[:2]:
        Rule('Gab1_binds_Grb2_'+erb.name, Gab1(grb2=None,atp=None,shp2=None,erk=None, state='up') +
             Grb2(sos=None, erb=2,gab1=None) % erb(gs=2, comp='pm',cpp=None) <>
             Gab1(grb2=1,atp=None,state='up', erk=None, shp2=None) % Grb2(sos=None, erb=2, gab1=1) % erb(gs=2, comp='pm',cpp=None),
             k105, kd105)

    ## v30-v36, v815-v821
    ## Gab1 + ATP <-> Gab1:ATP -> Gab1~P + ATP
    catalyze(ATP(erb=None), 'gab1', Gab1(state='up',grb2=ANY, shp2=None,erk=None), 'atp', Gab1(state='p',grb2=ANY, shp2=None,erk=None),
             (k122_gab, kd122_gab, kd123_gab))

def bind_PI3K():
    " v621-v627 "
    " PI3K binds scaffolding protein Gab1~P "
    " yet to account for reactions with rc k67, kd67 "
    
    # Initial amount
    # ==============
    Parameter('PI3K_0', 3.55656e+7)    # c287
    # Rate constants
    # ==============
    Parameter('k66', 1.5e-5)   # k66  # K67 and kd67 also used for a subset of rxns, no pattern observed :(
    Parameter('kd66', 0.2)
    Parameter('k67', 5e-5)
    Parameter('kd67', 0.02)

    alias_model_components()
    
    # Initial conditions
    # ==============
    Initial(PI3K(gab1=None, pip2=None, ras=None), PI3K_0)

    # Rules
    # ======
    # This was almost a nice single rule, except a few of the species need a
    # different rate.
    for erb, other_erbs in (ErbB1, receptors), (ErbB2, receptors[1:]):
        for other_erb in other_erbs:
            rates = (k66, kd66)
            if ((erb is ErbB2 and (other_erb is ErbB2 or other_erb is ErbB3)) or
                (erb is ErbB1 and other_erb is ErbB3)):
                rates = (k67, kd67)
            Rule('_'.join((erb.name, other_erb.name, 'bind_gab1_pI3k')),
                 erb() % other_erb() % Gab1(state='p', shp2=None, erk=None, pi3k=None) + PI3K(gab1=None, ras=None, pip2=None) <>
                 erb() % other_erb() % Gab1(state='p', shp2=None, erk=None, pi3k=1) % PI3K(gab1=1, ras=None, pip2=None),
                 *rates)

def cox2_drugs_init(ibuprofen=False):

    if ibuprofen:
        Monomer('IBU', ['b']) #Ibuprofen
        Parameter('IBU_0', 180) #Micromolar
        alias_model_components()
        Initial(IBU(b=None), IBU_0)

def effectors_bind_anti_apoptotics():
    """
    Slightly modified from lopez_modules.embedded version to add that Bcl2 cannot be phosphorylated on S70 and have anti-apoptotic activity. (These interactions turned on in crosstalk modules).    
    Binding of Bax and Bak to Bcl2, BclxL, and Mcl1.

    Affinities of Bak for Bcl-xL and Mcl-1 are taken from Willis et al.

    Preferential affinity of Bax for Bcl-2 and Bcl-xL were taken from Zhai et
    al.  Bax:Bcl2 and Bax:Bcl-xL affinities were given order of magnitude
    estimates of 10nM.

    See comments on units for :py:func:`tBid_binds_all_anti_apoptotics`.

    Willis, S. N., Chen, L., Dewson, G., Wei, A., Naik, E., Fletcher, J. I.,
    Adams, J. M., et al. (2005). Proapoptotic Bak is sequestered by Mcl-1 and
    Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins. Genes &
    Development, 19(11), 1294-1305. `doi:10.1101/gad.1304105`

    Zhai, D., Jin, C., Huang, Z., Satterthwait, A. C., & Reed, J. C. (2008).
    Differential regulation of Bax and Bak by anti-apoptotic Bcl-2 family
    proteins Bcl-B and Mcl-1. The Journal of biological chemistry, 283(15),
    9580-9586.  `doi:10.1074/jbc.M708426200`
    """

    alias_model_components()
    bind_table([[                            Bcl2(S70='U'),  BclxL(state='M'),         Mcl1],
                [Bax(active_monomer), 10e-9*N_A*V,       10e-9*N_A*V,         None],
                [Bak(active_monomer),        None,       50e-9*N_A*V,  10e-9*N_A*V]],
               kf=1e6/(N_A*V))

def rec_events_inh_ERL():
    """Receptor events involving the EGFR kinase inhibitor erlotinib.  Binds in the ATP binding pocket."""
    alias_model_components()
    
    #Binding of erlotinib to EGFR
    #Assumption here: erlotinib only binds to dimers and its ligand binding status doesn't matter (need to check this)
    bind(erbb(ty='1', bd=ANY, st='U', loc='C'), 'b', ERL(), 'b', par['EGFR_bind_ERL'])