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)