Default initial conditions

Proteins

Our default state for unknown initial protein concentrations and states is to iterate over all of the Monomer objects in their default state and assign them an initial condition of 1e-8 (10 nanomolar). This allows certain analytical procedures that depend on initial conditions to be run.

Afterwards, we fill in more specific concentration information below.

from pysb import Parameter, Initial

# Iterate over every monomer
for m in model.monomers:
    states_dict = {}
    # Iterate over every site in the monomer
    for s in m.sites:
        # If it's in the site states dict, assign it the first of the
        # listed states
        if s in m.site_states:
            states_dict[s] = m.site_states[s][0]
        # Otherwise (e.g., the site is used only for binding) assign it
        # a state None, meaning unbound:
        else:
            states_dict[s] = None

    # Create the initial condition parameter based on the protein name
    initial_value = Parameter('{0}_0'.format(m.name), 1.0e-8)

    # Create the initial condition
    Initial(m(**states_dict), initial_value)

Nucleotides

For the concentration of NTPs:

[PMID7877593]: The concentrations of bases, nucleosides, and nucleosides mono-, di- and tri-phosphate are compared for about 600 published values. The data are predominantly from mammalian cells and fluids. For the most important ribonucleotides, average concentrations + SD (uM) are: ATP, 3,152 + 1,698; GTP, 468 + 224;...For deoxynucleosides-triphosphate (dNTP), the concentrations in dividing cells are: dATP, 24 + 22; dGTP, 5.2 + 4.5;... For the 4 dNTPs, tumor cells have concentrations of 6–11 fold over normal cells, and for the 4 NTPs, tumor cells also have concentrations 1.2-5 fold over the normal cells.

GTP_0.value = 468e-6

For the time being, we assume a ten-fold lower value for GDP:

GDP_0.value = GTP_0.value / 10.

For simulations involving a labeled nucleotide (as in the experiments of Wittinghofer in [PMID2200519] and [PMID9585556]), we explicitly declare these here as having an initial condition of 0 so that they can be set for specific simulations later:

Parameter('mGTP_0', 0.)
Initial(GTP(p=None, label='y'), mGTP_0)

Parameter('mGDP_0', 0.)
Initial(GDP(p=None, label='y'), mGDP_0)

References

[PMID7877593]

Traut TW. Physiological concentrations of purines and pyrimidines. Mol Cell Biochem. 1994 Nov 9;140(1):1-22. PMID:7877593 PDF