def aa_count(filename, filetype):
res_dict = {}
f = open(filename)
for record in SeqIO.parse(f, filetype):
temp_dict = ProteinAnalysis(str(record.seq)).count_amino_acids()
for key, val in temp_dict.items():
if key in res_dict:
res_dict[key] = res_dict[key] + val
else:
res_dict[key] = val
return res_dict
def add_prot_metabolism(model):
prot_metab_rxns = []
added_mets = []
print('Model name:', model.name)
print('1. Adding tRNAs ...')
tRNA = Metabolite(id='tRNA_c',
formula = '',
name= 'tRNA',
compartment='c')
tRNA_synthesis = Reaction(id= 'EX_tRNA',
name= 'tRNA synthesis(exchange)',
subsystem= 'tRNA metabolism',
lower_bound=-INF,
upper_bound= INF)
tRNA_synthesis.add_metabolites({tRNA: 1})
model.add_reaction(tRNA_synthesis)
prot_metab_rxns.append(tRNA_synthesis.id)
added_mets.append(tRNA)
print('2. Adding Aminoacyl-tRNAs synthesis pathways...')
ppi_c = model.metabolites.ppi_c
pi_c = model.metabolites.pi_c
atp_c = model.metabolites.atp_c
adp_c = model.metabolites.adp_c
amp_c = model.metabolites.adp_c
aa_list = ['tyr_L_c','trp_L_c','thr_L_c','leu_L_c','ile_L_c','lys_L_c','ala_L_c','val_L_c','met_L_c','ser_L_c',
'asp_L_c','gly_c','pro_L_c','cys_L_c','glu_L_c','gln_L_c','arg_L_c','phe_L_c','his_L_c','asn_L_c']
for aa in aa_list:
Aminoacyl_tRNA = Metabolite(id= aa[0:3]+"_tRNA_c",
formula='',
name= "amminoacyl_"+aa+"_tRNA",
compartment='c')
aa_tRNA_synth = Reaction(id= aa[0:3]+'_tRNA_synth',
name=aa[0:3]+' tRNA synthesis',
subsystem='protein synthesis',
lower_bound= -INF,
upper_bound= INF)
aa_tRNA_synth.add_metabolites({
model.metabolites.get_by_id(aa): -1,
atp_c : -1,
tRNA : -1,
Aminoacyl_tRNA : 1,
ppi_c : 1,
amp_c : 1
})
model.add_reaction(aa_tRNA_synth)
prot_metab_rxns.append(aa_tRNA_synth.id)
added_mets.append(Aminoacyl_tRNA)
print('3. Adding muscle proteins synthesis pathways...')
uniprot_id = ['P68133', # actin
'P12882', # myosin heavy chain I and IIx
'Q9UKX2', # myosin heavy chain IIa
'Q9Y623', # myosin heavy chain IIb
'Q96A32', # myosin light chain type 2
'P05976', # myosin light chain type 1
'Q9H1R3', # myosin light chain kinase
'P09493', # tropomyosin type 1 (slow)
'P67936', # tropomyosin type 2 (fast)
'P63316', # troponin C type 1 (slow)
'P02585', # troponin C type 2 (fast)
'P19237', # troponin I type 1 (slow)
'P48788', # troponin I type 2 (fast)
'P13805', # troponin T type 1 (slow)
'P45378', # troponin T type 1 (fast)
]
translate_1to3 = {'A': 'ala',
'R': 'arg',
'N': 'asn',
'D': 'asp',
'C': 'cys',
'Q': 'gln',
'E': 'glu',
'G': 'gly',
'H': 'his',
'I': 'ile',
'L': 'leu',
'K': 'lys',
'M': 'met',
'F': 'phe',
'P': 'pro',
'S': 'ser',
'T': 'thr',
'W': 'trp',
'Y': 'tyr',
'V': 'val' }
MW = []
for prot_id in uniprot_id:
with ExPASy.get_sprot_raw(prot_id) as handle: #<--- why so slow???
Seq_record = SeqIO.read(handle, 'swiss')
handle.close()
print('Adding: '+ Seq_record.description.split('=')[1].split(';')[0] )
MW.append(SeqUtils.molecular_weight(Seq_record.seq, 'protein'))
aa_count = ProteinAnalysis((str(Seq_record.seq)),True).count_amino_acids()
protein = Metabolite(id=Seq_record.name[0:5]+'_protein_c',
formula='',
name = Seq_record.description.split()[1].split('=')[1],
compartment='c')
protein_synth = Reaction(id=Seq_record.name[0:5]+'_protein_synth',
name=Seq_record.description.split()[1].split('=')[1]+' synthesis',
subsystem='protein metabolism',
lower_bound= -INF,
upper_bound= INF)
model.add_metabolites([protein])
model.add_reaction(protein_synth)
stoich = {translate_1to3[k]+'_tRNA_c':-v for k,v in aa_count.items()}
stoich2 = {atp_c.id: -(len(str(Seq_record.seq))),
pi_c.id: (len(str(Seq_record.seq))),
adp_c.id: (len(str(Seq_record.seq))),
tRNA.id: (len(str(Seq_record.seq))),
protein.id: 1}
stoich.update(stoich2)
protein_synth.add_metabolites(stoich)
prot_metab_rxns.append(protein_synth.id)
added_mets.append(protein)
print('4. Adding muscle fibers synthesis pathways...')
actin = model.metabolites.ACTS__protein_c
myosinHC1 = model.metabolites.MYH1__protein_c
myosinHC2a = model.metabolites.MYH2__protein_c
myosinHC2b = model.metabolites.MYH4__protein_c
myosinLC2 = model.metabolites.MLRS__protein_c
myosinLC1 = model.metabolites.MYL1__protein_c
myosinK = model.metabolites.MYLK2_protein_c
tropomyosin1 = model.metabolites.TPM1__protein_c
tropomyosin2 = model.metabolites.TPM4__protein_c
troponinC1 = model.metabolites.TNNC1_protein_c
troponinC2 = model.metabolites.TNNC2_protein_c
troponinI1 = model.metabolites.TNNI1_protein_c
troponinI2 = model.metabolites.TNNI2_protein_c
troponinT1 = model.metabolites.TNNT1_protein_c
troponinT2 = model.metabolites.TNNT3_protein_c
# Myosin Type 1 muscle fiber : 2 myosinHC1 + 2 myosinK + 2 myosinLC1 -> 1 myo_fiber_1
myo_fiber_1 = Metabolite(id='myo_fiber_1_c',
formula= '',
name='Myosin fiber Type I',
compartment = 'c')
myo_fiber_1_synth = Reaction(id='myo_fiber_1_synth',
name='Myosin fiber Type 1 synthesis',
subsystem = 'protein metabolism',
lower_bound = -INF,
upper_bound = INF)
myo_fiber_1_synth.add_metabolites({
myosinHC1: -2,
myosinK: -2,
myosinLC1:-2,
myo_fiber_1: 1})
model.add_reaction(myo_fiber_1_synth)
prot_metab_rxns.append(myo_fiber_1_synth.id)
added_mets.append(myo_fiber_1)
# Myosin Type 2a muscle fiber: 2 myosinHC2a + 2 myosinK + 2 myosinLC2 -> 1 myo_fiber_2a
myo_fiber_2a = Metabolite(id='myo_fiber_2a_c',
formula= '',
name='Myosin fiber Type IIa',
compartment = 'c')
myo_fiber_2a_synth = Reaction(id='myo_fiber_2a_synth',
name='Myosin fiber Type 2a synthesis',
subsystem = 'protein metabolism',
lower_bound = -INF,
upper_bound = INF)
myo_fiber_2a_synth.add_metabolites({
myosinHC2a: -2,
myosinK: -2,
myosinLC2:-2,
myo_fiber_2a: 1})
model.add_reaction(myo_fiber_2a_synth)
prot_metab_rxns.append(myo_fiber_2a_synth.id)
added_mets.append(myo_fiber_2a)
# Myosin Type 2b muscle fiber: 2 myosinHC2b + 2 myosinK + 2 myosinLC2 -> 1 myo_fiber_2b
myo_fiber_2b = Metabolite(id='myo_fiber_2b_c',
formula= '',
name='Myosin fiber Type IIb',
compartment = 'c')
myo_fiber_2b_synth = Reaction(id='myo_fiber_2b_synth',
name='Myosin fiber Type 2b synthesis',
subsystem = 'protein metabolism',
lower_bound = -INF,
upper_bound = INF)
myo_fiber_2b_synth.add_metabolites({
myosinHC2b: -2,
myosinK: -2,
myosinLC2:-2,
myo_fiber_2b: 1})
model.add_reaction(myo_fiber_2b_synth)
prot_metab_rxns.append(myo_fiber_2b_synth.id)
added_mets.append(myo_fiber_2b)
# Myosin Type 2x muscle fiber : 2 myosinHC1 + 2 myosinK + 2 myosinLC2 -> 1 myo_fiber_2x
myo_fiber_2x = Metabolite(id='myo_fiber_2x_c',
formula= '',
name='Myosin fiber Type IIx',
compartment = 'c')
myo_fiber_2x_synth = Reaction(id='myo_fiber_2x_synth',
name='Myosin fiber Type 2x synthesis',
subsystem = 'protein metabolism',
lower_bound = -INF,
upper_bound = INF)
myo_fiber_2x_synth.add_metabolites({
myosinHC1: -2,
myosinK: -2,
myosinLC2:-2,
myo_fiber_2x: 1})
model.add_reaction(myo_fiber_2x_synth)
prot_metab_rxns.append(myo_fiber_2x_synth.id)
added_mets.append(myo_fiber_2x)
# Tropomyosin Type 1 complex: 2 tropomyosin1 -> 1 tropo_myo_fiber_1
tropo_myo_fiber_1 = Metabolite(id="tropo_myo_fiber_1_c",
formula='',
name="Tropomyosin Type 1 complex",
compartment= 'c')
tropo_myo_fiber_1_synth = Reaction(id="tropo_myo_fiber_1_synth",
name="Troponin type I complex synthesis",
subsystem='protein metabolism',
upper_bound= INF,
lower_bound= -INF)
tropo_myo_fiber_1_synth.add_metabolites({
tropomyosin1: -2,
tropo_myo_fiber_1: 1})
model.add_reaction(tropo_myo_fiber_1_synth)
prot_metab_rxns.append(tropo_myo_fiber_1_synth.id)
added_mets.append(tropo_myo_fiber_1)
# Tropomyosin Type 2 complex: 2 tropomyosin2 -> 1 tr_myo_fiber_2
tropo_myo_fiber_2 = Metabolite(id="tropo_myo_fiber_2_c",
formula='',
name="Tropomyosin Type 2 complex",
compartment= 'c')
tropo_myo_fiber_2_synth = Reaction(id="tropo_myo_fiber_2_synth",
name="Troponin type II complex synthesis",
subsystem='protein metabolism',
upper_bound= INF,
lower_bound= -INF)
tropo_myo_fiber_2_synth.add_metabolites({
tropomyosin2: -2,
tropo_myo_fiber_2: 1})
model.add_reaction(tropo_myo_fiber_2_synth)
prot_metab_rxns.append(tropo_myo_fiber_2_synth.id)
added_mets.append(tropo_myo_fiber_2)
# Troponin complex Type 1: 1 troponinC1 + 1 troponinI1 + 1 troponinT1 -> 1 tropo_complex_1
tropo_complex_1= Metabolite(id="tropo_complex_1_c",
formula='',
name="Troponin Type 1 complex",
compartment= 'c')
troponin_1_synth = Reaction(id="troponin_1_synth",
name="Troponin I complex synthesis",
subsystem='protein metabolism',
upper_bound= INF,
lower_bound= -INF)
troponin_1_synth.add_metabolites({
troponinC1: -1,
troponinI1: -1,
troponinT1: -1,
tropo_complex_1:1})
model.add_reaction(troponin_1_synth)
prot_metab_rxns.append(troponin_1_synth.id)
added_mets.append(tropo_complex_1)
# Troponin complex Type 2: 1 troponinC2 + 1 troponinI2 + 1 troponinT2 -> 1 tropo_complex_2
tropo_complex_2= Metabolite(id="tropo_complex_2_c",
formula='',
name="Troponin Type 2 complex",
compartment= 'c')
troponin_2_synth = Reaction(id="troponin_2_synth",
name="Troponin II complex synthesis",
subsystem='protein metabolism',
upper_bound= INF,
lower_bound= -INF)
troponin_2_synth.add_metabolites({
troponinC2: -1,
troponinI2: -1,
troponinT2: -1,
tropo_complex_2:1})
model.add_reaction(troponin_2_synth)
prot_metab_rxns.append(troponin_2_synth.id)
added_mets.append(tropo_complex_2)
# Contractile unit type 1 : 7 actin + 7 myo_fiber_1 + 1 tropo_myo_fiber_1 + 1 tropo_complex_1 -> 1 contr_unit_1
contr_unit_1 = Metabolite(id='contr_unit_1_c',
formula = '',
name='myofiber contractile unit type I',
compartment='c')
contr_unit_1_synth = Reaction(id='contr_unit_I_synth',
name='Synthesis of myofiber contractile unit type I',
subsystem= 'protein metabolism',
upper_bound= INF,
lower_bound= -INF)
contr_unit_1_synth.add_metabolites({
actin:-7,
myo_fiber_1: -7,
tropo_myo_fiber_1:-1,
tropo_complex_1:-1,
contr_unit_1:1})
model.add_reaction(contr_unit_1_synth)
###prot_metab_rxns.append(contr_unit_1_synth.id)
added_mets.append(contr_unit_1)
# Contractile unit type 2a: 7 actin + 7 myo_fiber_2a + 1 tropo_myo_fiber_2 + 1 tropo_complex_2 -> 1 contr_unit_2a
contr_unit_2a = Metabolite(id='contr_unit_2a_c',
formula = '',
name='myofiber contractile unit type IIa',
compartment='c')
contr_unit_2a_synth = Reaction(id='contr_unit_IIa_synth',
name='Synthesis of myofiber contractile unit type IIa',
subsystem= 'protein metabolism',
upper_bound= INF,
lower_bound= -INF)
contr_unit_2a_synth.add_metabolites({
actin:-7,
myo_fiber_2a: -7,
tropo_myo_fiber_2:-1,
tropo_complex_2:-1,
contr_unit_2a:1})
model.add_reaction(contr_unit_2a_synth)
###prot_metab_rxns.append(contr_unit_2a_synth.id)
added_mets.append(contr_unit_2a)
# Contractile unit type 2b: 7 actin + 7 myo_fiber_2b + 1 tropo_myo_fiber_2 + 1 tropo_complex_2 -> 1 contr_unit_2b
contr_unit_2b = Metabolite(id='contr_unit_2b_c',
formula = '',
name='myofiber contractile unit type IIb',
compartment='c')
contr_unit_2b_synth = Reaction(id='contr_unit_IIb_synth',
name='Synthesis of myofiber contractile unit type IIb',
subsystem= 'protein metabolism',
upper_bound= INF,
lower_bound= -INF)
contr_unit_2b_synth.add_metabolites({
actin:-7,
myo_fiber_2b: -7,
tropo_myo_fiber_2:-1,
tropo_complex_2:-1,
contr_unit_2b:1})
model.add_reaction(contr_unit_2b_synth)
###prot_metab_rxns.append(contr_unit_2b_synth.id)
added_mets.append(contr_unit_2b)
# Contractile unit type 2x: 7 actin + 7 myo_fiber_2x + 1 tropo_myo_fiber_2 + 1 tropo_complex_2 -> 1 contr_unit_2x
contr_unit_2x = Metabolite(id='contr_unit_2x_c',
formula = '',
name='myofiber contractile unit type IIx',
compartment='c')
contr_unit_2x_synth = Reaction(id='contr_unit_IIx_synth',
name='Synthesis of myofiber contractile unit type IIx',
subsystem= 'protein metabolism',
upper_bound= INF,
lower_bound= -INF)
contr_unit_2x_synth.add_metabolites({
actin:-7,
myo_fiber_2x: -7,
tropo_myo_fiber_2:-1,
tropo_complex_2:-1,
contr_unit_2x:1})
model.add_reaction(contr_unit_2x_synth)
###prot_metab_rxns.append(contr_unit_2x_synth.id)
added_mets.append(contr_unit_2x)
'''
print('5. Adding contractile units accumulation... (sink reactions)')
# Contractile unit 1 sink: contr_unit_1 ->
contr_unit_1_storage = Reaction(id='contr_unit_1_storage',
name='contractile unit type 1 storage (sink)',
subsystem='protein metabolism_',
upper_bound= INF,
lower_bound=-INF)
contr_unit_1_storage.add_metabolites({
contr_unit_1: -1
})
model.add_reaction(contr_unit_1_storage)
prot_metab_rxns.append(contr_unit_1_storage.id)
# Contractile unit 2a sink: contr_unit_2a ->
contr_unit_2a_storage = Reaction(id='contr_unit_2a_storage',
name='contractile unit type 2a storage (sink)',
subsystem='protein metabolism_',
upper_bound= INF,
lower_bound=-INF)
contr_unit_2a_storage.add_metabolites({
contr_unit_2a: -1
})
model.add_reaction(contr_unit_2a_storage)
prot_metab_rxns.append(contr_unit_2a_storage.id)
# Contractile unit 2b sink: contr_unit_2b ->
contr_unit_2b_storage = Reaction(id='contr_unit_2b_storage',
name='contractile unit type 2b storage (sink)',
subsystem='protein metabolism_',
upper_bound= INF,
lower_bound=-INF)
contr_unit_2b_storage.add_metabolites({
contr_unit_2b: -1
})
model.add_reaction(contr_unit_2b_storage)
prot_metab_rxns.append(contr_unit_2b_storage.id)
# Contractile unit 2x sink: contr_unit_2x ->
contr_unit_2x_storage = Reaction(id='contr_unit_2x_storage',
name='contractile unit type 2x storage (sink)',
subsystem='protein metabolism_',
upper_bound= INF,
lower_bound=-INF)
contr_unit_2x_storage.add_metabolites({
contr_unit_2x: -1
})
model.add_reaction(contr_unit_2x_storage)
prot_metab_rxns.append(contr_unit_2x_storage.id)
'''
print('5. Add contractile fibers accumulation (storage)*')
myofibers_storage = Reaction(id='myofibers_storage',
name='contractile units storage (sink)',
subsystem='protein metabolism_',
upper_bound= INF,
lower_bound=-INF)
myofibers_storage.add_metabolites({
contr_unit_1: -1,
contr_unit_2a: -1,
contr_unit_2b: -1,
contr_unit_2x: -1
})
model.add_reaction(myofibers_storage)
prot_metab_rxns.append(myofibers_storage.id)
print('Adding ATP_expenditure reaction...')
pi = model.metabolites.pi_c
atp = model.metabolites.atp_c
adp = model.metabolites.adp_c
ATP_expenditure = Reaction(id= 'ATP_expenditure',
name= 'Total energy expenditure',
subsystem = 'energy metabolism',
upper_bound = INF,
lower_bound = -INF)
ATP_expenditure.add_metabolites({
atp: -1,
adp: 1,
pi: 1})
model.add_reaction(ATP_expenditure)
print('----------------------------------------')
print(len(prot_metab_rxns)+4, "reactions have been added to the model")
print(len(added_mets), "metabolites have been added to the model")
print( 'All done!')
print('----------------------------------------')
return MW , prot_metab_rxns
