def chen_febs_direct(do_pore_assembly=True, do_pore_transport=False):
"""The "direct" model drawn from [Chen2007febs]_.
Model features (see the source code):
* Activation of Bax by an activator (tBid) in a one-step, hit-and-run
manner; Bax activation is reversible.
* Bcl-2 can bind tBid, but not Bax.
Parameters
----------
do_pore_assembly : True (default) or False
As for :py:func:`chen_biophys_j`.
do_pore_transport : True or False (default)
As for :py:func:`chen_biophys_j`.
"""
# Initial conditions
Parameter('Bcl2_0' , 30e-9) # Bcl2
Parameter('Bax_0' , 60e-9) # InBax
alias_model_components()
Initial(Bax(bf=None, s1=None, s2=None, state='C'), Bax_0)
Initial(Bcl2(bf=None), Bcl2_0)
# One-step "kiss-and-run" activation of Bax by tBid
catalyze_one_step_reversible(
Bid(state='T', bf=None), Bax(bf=None, **inactive_monomer),
Bax(bf=None, **active_monomer), [1e6/(N_A*V), 1e-3])
# Bcl2 binds tBid and Bad (a sensitizer) but not Bax
bind_table([[ Bcl2],
[Bid(state='T'), (1e5/(N_A*V), 1e-3)],
[Bad(state='M'), (1e5/(N_A*V), 1e-3)]])
if do_pore_assembly:
# Four Bax monomers cooperatively bind to form a tetramer
assemble_pore_spontaneous(Bax(state='A', bf=None),
[4*1e6/(N_A*V), 1e-3])
if do_pore_transport:
# Release Cytochrome C and Smac:
shen_pore_transport(pore_size=4)
def chen_febs_direct(do_pore_assembly=True, do_pore_transport=False):
"""The "direct" model drawn from [Chen2007febs]_.
Model features (see the source code):
* Activation of Bax by an activator (tBid) in a one-step, hit-and-run
manner; Bax activation is reversible.
* Bcl-2 can bind tBid, but not Bax.
Parameters
----------
do_pore_assembly : True (default) or False
As for :py:func:`chen_biophys_j`.
do_pore_transport : True or False (default)
As for :py:func:`chen_biophys_j`.
"""
# Initial conditions
Parameter('Bcl2_0', 30e-9 * N_A * V) # Bcl2
Parameter('Bax_0', 60e-9 * N_A * V) # InBax
alias_model_components()
Initial(Bax(bf=None, s1=None, s2=None, state='C'), Bax_0)
Initial(Bcl2(bf=None), Bcl2_0)
# One-step "kiss-and-run" activation of Bax by tBid
catalyze_one_step_reversible(Bid(state='T', bf=None),
Bax(bf=None, **inactive_monomer),
Bax(bf=None, **active_monomer),
[1e6 / (N_A * V), 1e-3])
# Bcl2 binds tBid and Bad (a sensitizer) but not Bax
bind_table([[Bcl2], [Bid(state='T'), (1e5 / (N_A * V), 1e-3)],
[Bad(state='M'), (1e5 / (N_A * V), 1e-3)]])
if do_pore_assembly:
# Four Bax monomers cooperatively bind to form a tetramer
assemble_pore_spontaneous(Bax(state='A', bf=None),
[4 * 1e6 / (N_A * V), 1e-3])
if do_pore_transport:
# Release Cytochrome C and Smac:
shen_pore_transport(pore_size=4)
def chen_biophys_j(do_pore_assembly=True, do_pore_transport=False):
"""Model drawn from [Chen2007biophysj]_.
Model features (see the source code):
* Activation of Bax by an activator (tBid) in a one-step, hit-and-run
manner; Bax activation is reversible.
* Bcl2 binds both tBid and Bax Bax can displace tBid from Bcl-2 (but not
the reverse).
* If Bax oligomerization is incorporated into the model (see
`do_pore_assembly` argument, below), then this occurs as a spontaneous,
order 4 reaction.
This model combines both "direct" type and "indirect" type elements in
that Bcl-2 is capable of binding both Bid and Bax (see `bind_table` call
in the source code).
Parameters
----------
do_pore_assembly : True (default) or False
If True, adds the formation of Bax oligomers to the model. If False,
the model's most downstream element is Bax activation. This is included
for two reasons: first, the original publication included two variant
models, one with and one without Bax oligomerization, so this allows
this aspect of the original models to be explored. Second, it allows
a model that extends this model to implement a different model of Bax
pore assembly (for example, as is the case with cui_direct).
do_pore_transport : True or False (default)
If True, adds the release of Cytochrome C and Smac to the model by
calling the function :py:func:`shen_pore_transport`. If CytoC/Smac
release are not incorporated into the model, the model matches the
originally published model but can't be composed into the full
extrinsic apoptosis pathway.
"""
Parameter('Bcl2_0', 0.1e-6 * N_A * V) # Mitochondrial Bcl2
Parameter('Bax_0', 0.2e-6 * N_A * V) # Bax
alias_model_components()
# Bax is in the Cytosolic, inactive state by default.
Initial(Bax(bf=None, s1=None, s2=None, state='C'), Bax_0)
Initial(Bcl2(bf=None), Bcl2_0)
# One-step "kiss-and-run" activation of Bax by tBid:
catalyze_one_step_reversible(
Bid(state='T', bf=None), Bax(bf=None, **inactive_monomer),
Bax(bf=None, **active_monomer), [0.5e6/(N_A*V), 1e-1])
# Bcl2 binds tBid and Bax:
bind_table([[ Bcl2],
[Bid(state='T'), (3e6/(N_A*V), 4e-2)],
[Bax(active_monomer), (2e6/(N_A*V), 1e-3)]])
# Bax can displace Bid from Bcl2:
displace(Bax(active_monomer), Bid(state='T'), Bcl2, 2e6/(N_A*V))
if do_pore_assembly:
# Four Bax monomers cooperatively bind to form a tetramer
assemble_pore_spontaneous(Bax(state='A', bf=None),
[2e6*4/(N_A*V), 0])
if do_pore_transport:
# Release Cytochrome C and Smac:
shen_pore_transport(pore_size=4)
def chen_biophys_j(do_pore_assembly=True, do_pore_transport=False):
"""Model drawn from [Chen2007biophysj]_.
Model features (see the source code):
* Activation of Bax by an activator (tBid) in a one-step, hit-and-run
manner; Bax activation is reversible.
* Bcl2 binds both tBid and Bax Bax can displace tBid from Bcl-2 (but not
the reverse).
* If Bax oligomerization is incorporated into the model (see
`do_pore_assembly` argument, below), then this occurs as a spontaneous,
order 4 reaction.
This model combines both "direct" type and "indirect" type elements in
that Bcl-2 is capable of binding both Bid and Bax (see `bind_table` call
in the source code).
Parameters
----------
do_pore_assembly : True (default) or False
If True, adds the formation of Bax oligomers to the model. If False,
the model's most downstream element is Bax activation. This is included
for two reasons: first, the original publication included two variant
models, one with and one without Bax oligomerization, so this allows
this aspect of the original models to be explored. Second, it allows
a model that extends this model to implement a different model of Bax
pore assembly (for example, as is the case with cui_direct).
do_pore_transport : True or False (default)
If True, adds the release of Cytochrome C and Smac to the model by
calling the function :py:func:`shen_pore_transport`. If CytoC/Smac
release are not incorporated into the model, the model matches the
originally published model but can't be composed into the full
extrinsic apoptosis pathway.
"""
Parameter('Bcl2_0', 0.1e-6 * N_A * V) # Mitochondrial Bcl2
Parameter('Bax_0', 0.2e-6 * N_A * V) # Bax
alias_model_components()
# Bax is in the Cytosolic, inactive state by default.
Initial(Bax(bf=None, s1=None, s2=None, state='C'), Bax_0)
Initial(Bcl2(bf=None), Bcl2_0)
# One-step "kiss-and-run" activation of Bax by tBid:
catalyze_one_step_reversible(Bid(state='T', bf=None),
Bax(bf=None, **inactive_monomer),
Bax(bf=None, **active_monomer),
[0.5e6 / (N_A * V), 1e-1])
# Bcl2 binds tBid and Bax:
bind_table([[Bcl2], [Bid(state='T'), (3e6 / (N_A * V), 4e-2)],
[Bax(active_monomer), (2e6 / (N_A * V), 1e-3)]])
# Bax can displace Bid from Bcl2:
displace(Bax(active_monomer), Bid(state='T'), Bcl2, 2e6 / (N_A * V))
if do_pore_assembly:
# Four Bax monomers cooperatively bind to form a tetramer
assemble_pore_spontaneous(Bax(state='A', bf=None),
[2e6 * 4 / (N_A * V), 0])
if do_pore_transport:
# Release Cytochrome C and Smac:
shen_pore_transport(pore_size=4)
