def add_dummy_reactions(me_model, dna_seq, update=True):
"""
Add all reactions necessary to produce a dummy reaction catalyzed by
"CPLX_dummy".
Parameters
----------
me_model : :class:`cobrame.core.model.MEModel`
The MEModel object to which the content will be added
dna_seq : str
DNA sequence of dummy gene. Should be representative of the average
codon composition, amino acid composition, length of a gene in the
organism being modeled
update : bool
If True, run update functions on all transcription, translation,
complex formation, and metabolic reactions added when constructing
dummy reactions.
"""
dummy = cobrame.StoichiometricData("dummy_reaction", me_model)
dummy.lower_bound = 0
dummy.upper_bound = 1000
dummy._stoichiometry = {'CPLX_dummy': -1}
create_transcribed_gene(me_model, 'dummy', 'mRNA', dna_seq)
add_transcription_reaction(me_model, "RNA_dummy", {"dummy"}, dna_seq)
me_model.add_metabolites(cobrame.TranslatedGene("protein_" + "dummy"))
add_translation_reaction(me_model,
"dummy",
dna_sequence=dna_seq,
update=update)
try:
complex_data = cobrame.ComplexData("CPLX_dummy", me_model)
except ValueError:
warn('CPLX_dummy already in model')
complex_data = me_model.process_data.get_by_id('CPLX_dummy')
complex_data.stoichiometry = {"protein_dummy": 1}
if update:
complex_data.create_complex_formation()
def update(self, verbose=True):
"""
Creates reaction using the associated translation data and adds
chemical formula to protein product
This function adds the following components to the reaction
stoichiometry (using 'data' as shorthand for
:class:`cobrame.core.processdata.TranslationData`):
1) Amino acids defined in data.amino_acid_sequence. Subtracting water
to account for condensation reactions during polymerization
2) Ribosome w/ translation coupling coefficient (if present)
3) mRNA defined in data.mRNA w/ translation coupling coefficient
4) mRNA + nucleotides + hydrolysis ATP cost w/ degradation coupling
coefficient (if kdeg (defined in model.global_info) > 0)
5) RNA_degradosome w/ degradation coupling coefficient (if present and
kdeg > 0)
6) Protein product defined in data.protein
7) Subreactions defined in data.subreactions
8) protein_biomass :class:`cobrame.core.component.Constraint`
corresponding to the protein product's mass
9) Subtract mRNA_biomass :class:`cobrame.core.component.Constraint`
defined by mRNA degradation coupling coefficinet (if kdeg > 0)
Parameters
----------
verbose : bool
Prints when new metabolites are added to the model when executing
update()
"""
self.clear_metabolites()
translation_data = self.translation_data
protein_id = translation_data.protein
mrna_id = translation_data.mRNA
protein_length = len(translation_data.amino_acid_sequence)
nucleotide_sequence = translation_data.nucleotide_sequence
model = self._model
metabolites = self._model.metabolites
new_stoichiometry = defaultdict(int)
# Set Parameters
kt = self._model.global_info['kt']
k_deg = self._model.global_info['k_deg']
r0 = self._model.global_info['r0']
m_rr = self._model.global_info['m_rr']
f_rrna = self._model.global_info['f_rRNA']
m_aa = self._model.global_info['m_aa']
m_nt = self._model.global_info['m_nt']
f_mrna = self._model.global_info['f_mRNA']
c_ribo = m_rr / f_rrna / m_aa
c_mrna = m_nt / f_mrna / m_aa
# -----------------Add Amino Acids----------------------------------
for aa, value in iteritems(translation_data.amino_acid_count):
new_stoichiometry[aa] = -value
new_stoichiometry['h2o_c'] += value
# Length protein - 1 dehydration reactions
new_stoichiometry['h2o_c'] -= 1.
# -----------------Add Ribosome Coupling----------------------------
try:
ribosome = metabolites.get_by_id("ribosome")
except KeyError:
warn("ribosome not found")
else:
k_ribo = mu * c_ribo * kt / (mu + kt * r0) # in hr-1
coupling = -protein_length * mu / k_ribo
new_stoichiometry[ribosome.id] = coupling
# -------------------Add mRNA Coupling------------------------------
try:
transcript = metabolites.get_by_id(mrna_id)
except KeyError:
# If transcript not found add to the model as the mRNA_id
warn("transcript ('%s') not found" % mrna_id)
transcript = \
cobrame.TranscribedGene(mrna_id, mrna_id, nucleotide_sequence)
model.add_metabolites(transcript)
# Calculate coupling constraints for mRNA and degradation
k_mrna = mu * c_mrna * kt / (mu + kt * r0) * 3. # 3 nucleotides per AA
rna_amount = mu / k_mrna
deg_amount = k_deg / k_mrna
# Add mRNA coupling to stoichiometry
new_stoichiometry[transcript.id] = -(rna_amount + deg_amount)
# ---------------Add Degradation Requirements -------------------------
# Add degraded nucleotides to stoichiometry
for nucleotide, count in iteritems(transcript.nucleotide_count):
new_stoichiometry[nucleotide] += count * deg_amount
# ATP hydrolysis required for cleaving
nucleotide_length = len(transcript.nucleotide_sequence)
# .25 ATP required per nucleotide hydrolysis
hydrolysis_amount = (nucleotide_length - 1) / 4. * deg_amount
atp_hydrolysis = {'atp_c': -1, 'h2o_c': -1, 'adp_c': 1,
'pi_c': 1, 'h_c': 1}
for metabolite, value in iteritems(atp_hydrolysis):
new_stoichiometry[metabolite] += hydrolysis_amount * value
# Add degradosome coupling, if known
try:
rna_degradosome = metabolites.get_by_id("RNA_degradosome")
except KeyError:
warn("RNA_degradosome not found")
else:
deg_coupling = -deg_amount * mu / 65. / 3600 # keff of degradosome
new_stoichiometry[rna_degradosome.id] = deg_coupling
# --------------- Add Protein to Stoichiometry ------------------------
# Added protein to model if not already included
try:
protein = metabolites.get_by_id(protein_id)
except KeyError:
protein = cobrame.TranslatedGene(protein_id)
model.add_metabolites(protein)
new_stoichiometry[protein.id] = 1
# ------- Convert ids to metabolites and add to model -----------------
# add subreactions to stoichiometry
new_stoichiometry = self.add_subreactions(self.translation_data.id,
new_stoichiometry)
# convert metabolite ids to cobra metabolites
object_stoichiometry = self.get_components_from_ids(new_stoichiometry,
verbose=verbose)
# add metabolites to reaction
self.add_metabolites(object_stoichiometry, combine=False)
# -------------Update Element Dictionary and Formula-------------------
self._add_formula_to_protein(translation_data, protein)
# ------------------ Add biomass constraints --------------------------
# add biomass constraint for protein translated
protein_mass = protein.mass # kDa
self.add_metabolites({metabolites.protein_biomass: protein_mass},
combine=False)
# RNA biomass consumed due to degradation
mrna_mass = transcript.mass # kDa
self.add_metabolites(
{metabolites.mRNA_biomass: (-mrna_mass * deg_amount)},
combine=False)