MAPK module with MEK inhibition¶

from pysb import Monomer, Rule, Parameter, Annotation, ANY, Initial, Observable
from pysb.macros import bind, _macro_rule, catalyze_state
from pysb.util import alias_model_components

def mapk_monomers():
    Monomer('MEK', ['s', 'erk', 'inh', 'state'], {'state': ['up', 'p']})
    Monomer('PP2A', ['mek'])
    Monomer('ERK', ['s', 'sos1', 'state'], {'state': ['up', 'p']})
    Monomer('DUSP', ['erk'])

    Parameter('ERK_0', 1e5)  # 1e3
    Parameter('DUSP_0', 1e3)
    Parameter('MEK_0', 1e5)
    Parameter('PP2A_0', 1e3)

    alias_model_components()

    Initial(ERK(s=None, sos1=None,  state='up'), ERK_0)
    Initial(DUSP(erk=None), DUSP_0)
    Initial(MEK(s=None, erk=None, inh=None, state='up'), MEK_0)
    Initial(PP2A(mek=None), MEK_0)

def RAF_activates_MEK():

    Parameter('k_bmf', 1)
    Parameter('k_bmr', 0.1)
    Parameter('k_bme', 3)

    alias_model_components()

    catalyze_state(RAF(vem=None), 'erk', MEK(), 's',
                   'state', 'up', 'p', (k_bmf, k_bmr, k_bme))

def MEK_phosphorylates_ERK():

    Parameter('k_mef', 1)
    Parameter('k_mer', 0.1)
    Parameter('k_mee', 10)

    alias_model_components()

    catalyze_state(MEK(s=None, state='p', inh=None), 'erk', ERK(), 's',
                   'state', 'up', 'p', (k_mef, k_mer, k_mee))

def PP2A_phosphatase():

    Parameter('k_pp2f', 1)
    Parameter('k_pp2r', 0.001)
    Parameter('k_pp2e', 10)

    alias_model_components()

    catalyze_state(PP2A(), 'mek', MEK(erk=None), 's', 'state', 'p', 'up',
                   (k_pp2f, k_pp2r, k_pp2e))


def DUSP_phosphatase():

    Parameter('k_dspf', 1)
    Parameter('k_dspr', 0.001)
    Parameter('k_dspe', 10)

    alias_model_components()

    catalyze_state(DUSP(), 'erk', ERK(sos1=None), 's', 'state', 'p', 'up',
                      (k_dspf, k_dspr, k_dspe))


def ERK_feedback():

    Parameter('k_epsf', 1e-4)
    Parameter('k_epsr', 0.1)
    Parameter('k_epse', 1)

    alias_model_components()

    catalyze_state(ERK(state='p', s=None), 'sos1', SOS1(ras=None, phos=None),
                   'mapk1', 'state', 'up', 'p', (k_epsf, k_epsr, k_epse))

def MEK_inhibitor():
    Monomer('Trametinib', ['mek'])

    Parameter('Trametinib_0', 0)

    Parameter('kf_btm', 1)
    Parameter('kr_btm', 1e-5)

    alias_model_components()

    Initial(Trametinib(mek=None), Trametinib_0)

    Rule('bind_Trametinib', Trametinib(mek=None) + MEK(inh=None) <>
         Trametinib(mek=1) % MEK(inh=1), kf_btm, kr_btm)