def handle(self, *args, **options):
self.options = options
if self.options['purge']:
Residue.objects.filter(
protein_conformation__protein__entry_name__endswith='_a',
protein_conformation__protein__family__parent__parent__name=
'Alpha').delete()
ProteinConformation.objects.filter(
protein__entry_name__endswith='_a',
protein__family__parent__parent__name='Alpha').delete()
Protein.objects.filter(
entry_name__endswith='_a',
family__parent__parent__name='Alpha').delete()
# Building protein and protconf objects for g protein structure in complex
scs = SignprotComplex.objects.all()
for sc in scs:
self.logger.info(
'Protein, ProteinConformation and Residue build for alpha subunit of {} is building'
.format(sc))
try:
# Alpha subunit
try:
alpha_protein = Protein.objects.get(
entry_name=sc.structure.pdb_code.index.lower() + '_a')
except:
alpha_protein = Protein()
alpha_protein.entry_name = sc.structure.pdb_code.index.lower(
) + '_a'
alpha_protein.accession = None
alpha_protein.name = sc.structure.pdb_code.index.lower(
) + '_a'
alpha_protein.sequence = sc.protein.sequence
alpha_protein.family = sc.protein.family
alpha_protein.parent = sc.protein
alpha_protein.residue_numbering_scheme = sc.protein.residue_numbering_scheme
alpha_protein.sequence_type = ProteinSequenceType.objects.get(
slug='mod')
alpha_protein.source = ProteinSource.objects.get(
name='OTHER')
alpha_protein.species = sc.protein.species
alpha_protein.save()
try:
alpha_protconf = ProteinConformation.objects.get(
protein__entry_name=sc.structure.pdb_code.index.lower(
) + '_a')
except:
alpha_protconf = ProteinConformation()
alpha_protconf.protein = alpha_protein
alpha_protconf.state = ProteinState.objects.get(
slug='active')
alpha_protconf.save()
pdbp = PDBParser(PERMISSIVE=True, QUIET=True)
s = pdbp.get_structure('struct',
StringIO(sc.structure.pdb_data.pdb))
chain = s[0][sc.alpha]
nums = []
for res in chain:
try:
res['CA']
nums.append(res.get_id()[1])
except:
pass
resis = Residue.objects.filter(
protein_conformation__protein=sc.protein)
num_i = 0
temp_seq2 = ''
pdb_num_dict = OrderedDict()
# Create first alignment based on sequence numbers
for n in nums:
if sc.structure.pdb_code.index == '6OIJ' and n < 30:
nr = n + 6
else:
nr = n
pdb_num_dict[n] = [chain[n], resis.get(sequence_number=nr)]
# Find mismatches
mismatches = []
for n, res in pdb_num_dict.items():
if AA[res[0].get_resname()] != res[1].amino_acid:
mismatches.append(res)
pdb_lines = sc.structure.pdb_data.pdb.split('\n')
seqadv = []
for l in pdb_lines:
if l.startswith('SEQADV'):
seqadv.append(l)
mutations, shifted_mutations = OrderedDict(), OrderedDict()
# Search for annotated engineered mutations in pdb SEQADV
for s in seqadv:
line_search = re.search(
'SEQADV\s{1}[A-Z\s\d]{4}\s{1}([A-Z]{3})\s{1}([A-Z]{1})\s+(\d+)[\s\S\d]{5}([\s\S\d]{12})([A-Z]{3})\s+(\d+)(\s\S+)',
s)
if line_search != None:
if line_search.group(2) == sc.alpha:
if line_search.group(
4).strip() == sc.protein.accession:
if line_search.group(3) == line_search.group(
6):
mutations[int(line_search.group(3))] = [
line_search.group(1),
line_search.group(5)
]
else:
shifted_mutations[int(
line_search.group(3))] = [
line_search.group(1),
line_search.group(5),
int(line_search.group(6))
]
else:
# Exception for 6G79
if line_search.group(3) != line_search.group(
6) and 'CONFLICT' in line_search.group(
7):
mutations[int(line_search.group(3))] = [
line_search.group(1),
line_search.group(5)
]
# Exception for 5G53
if line_search.group(
4).strip() != sc.protein.accession:
mutations[int(line_search.group(3))] = [
line_search.group(1),
line_search.group(5)
]
remaining_mismatches = []
# Check and clear mismatches that are registered in pdb SEQADV as engineered mutation
for m in mismatches:
num = m[0].get_id()[1]
if num in mutations:
if m[0].get_resname() != mutations[num][0] and m[
1].amino_acid != AA[mutations[num][1]]:
remaining_mismatches.append(m)
elif num in shifted_mutations:
remaining_mismatches.append(m)
else:
remaining_mismatches.append(m)
### sanity check
# print(mutations)
# print(shifted_mutations)
# print(mismatches)
# print(remaining_mismatches)
# pprint.pprint(pdb_num_dict)
# Mismatches remained possibly to seqnumber shift, making pairwise alignment to try and fix alignment
if len(remaining_mismatches
) > 0 and sc.structure.pdb_code.index not in [
'6OIJ', '6OY9', '6OYA'
]:
ppb = PPBuilder()
seq = ''
for pp in ppb.build_peptides(chain, aa_only=False):
seq += str(pp.get_sequence())
pw2 = pairwise2.align.localms(sc.protein.sequence, seq, 2,
-1, -.5, -.1)
ref_seq, temp_seq = str(pw2[0][0]), str(pw2[0][1])
wt_pdb_dict = OrderedDict()
pdb_wt_dict = OrderedDict()
j, k = 0, 0
for i, ref, temp in zip(range(0, len(ref_seq)), ref_seq,
temp_seq):
if ref != '-' and temp != '-':
wt_pdb_dict[resis[j]] = pdb_num_dict[nums[k]]
pdb_wt_dict[pdb_num_dict[nums[k]][0]] = resis[j]
j += 1
k += 1
elif ref == '-':
wt_pdb_dict[i] = pdb_num_dict[nums[k]]
pdb_wt_dict[pdb_num_dict[nums[k]][0]] = i
k += 1
elif temp == '-':
wt_pdb_dict[resis[j]] = i
pdb_wt_dict[i] = resis[j]
j += 1
for i, r in enumerate(remaining_mismatches):
# Adjust for shifted residue when residue is a match
if r[0].get_id()[1] - remaining_mismatches[
i - 1][0].get_id()[1] > 1:
pdb_num_dict[r[0].get_id()[1] -
1][1] = pdb_wt_dict[chain[
r[0].get_id()[1] - 1]]
# Adjust for shifted residue when residue is mutated and it's logged in SEQADV
if r[0].get_id()[1] in shifted_mutations:
pdb_num_dict[r[0].get_id()[1]][1] = resis.get(
sequence_number=shifted_mutations[
r[0].get_id()[1]][2])
# Adjust for shift
else:
pdb_num_dict[r[0].get_id()[1]][1] = pdb_wt_dict[
r[0]]
bulked_residues = []
for key, val in pdb_num_dict.items():
# print(key, val) # sanity check
res_obj = Residue()
res_obj.sequence_number = val[0].get_id()[1]
res_obj.amino_acid = AA[val[0].get_resname()]
res_obj.display_generic_number = val[
1].display_generic_number
res_obj.generic_number = val[1].generic_number
res_obj.protein_conformation = alpha_protconf
res_obj.protein_segment = val[1].protein_segment
bulked_residues.append(res_obj)
Residue.objects.bulk_create(bulked_residues)
self.logger.info(
'Protein, ProteinConformation and Residue build for alpha subunit of {} is finished'
.format(sc))
except Exception as msg:
print(
'Protein, ProteinConformation and Residue build for alpha subunit of {} has failed'
.format(sc))
print(msg)
self.logger.info(
'Protein, ProteinConformation and Residue build for alpha subunit of {} has failed'
.format(sc))
def can_create_arrestins(self, family, residue_numbering_scheme, accession,
uniprot):
# get/create protein source
try:
source, created = ProteinSource.objects.get_or_create(
name=uniprot['source'], defaults={'name': uniprot['source']})
if created:
self.logger.info('Created protein source ' + source.name)
except IntegrityError:
source = ProteinSource.objects.get(name=uniprot['source'])
# get/create species
try:
species, created = Species.objects.get_or_create(
latin_name=uniprot['species_latin_name'],
defaults={
'common_name': uniprot['species_common_name'],
})
if created:
self.logger.info('Created species ' + species.latin_name)
except IntegrityError:
species = Species.objects.get(
latin_name=uniprot['species_latin_name'])
# get/create protein sequence type
# Wild-type for all sequences from source file
try:
sequence_type, created = ProteinSequenceType.objects.get_or_create(
slug='wt', defaults={
'slug': 'wt',
'name': 'Wild-type',
})
if created:
self.logger.info('Created protein sequence type Wild-type')
except:
self.logger.error(
'Failed creating protein sequence type Wild-type')
# create protein
p = Protein()
p.family = family
p.species = species
p.source = source
p.residue_numbering_scheme = residue_numbering_scheme
p.sequence_type = sequence_type
if accession:
p.accession = accession
p.entry_name = uniprot['entry_name'].lower()
p.name = uniprot['names'][0]
p.sequence = uniprot['sequence']
try:
p.save()
self.logger.info('Created protein {}'.format(p.entry_name))
except:
self.logger.error('Failed creating protein {}'.format(
p.entry_name))
# protein aliases
for i, alias in enumerate(uniprot['names']):
pcan = Protein.objects.get(
entry_name=uniprot['entry_name'].lower())
a = ProteinAlias()
a.protein = pcan
a.name = alias
a.position = i
try:
a.save()
self.logger.info('Created protein alias ' + a.name +
' for protein ' + p.name)
except:
self.logger.error('Failed creating protein alias ' + a.name +
' for protein ' + p.name)
# genes
for i, gene in enumerate(uniprot['genes']):
g = False
try:
g, created = Gene.objects.get_or_create(name=gene,
species=species,
position=i)
if created:
self.logger.info('Created gene ' + g.name +
' for protein ' + p.name)
except IntegrityError:
g = Gene.objects.get(name=gene, species=species, position=i)
if g:
pcan = Protein.objects.get(
entry_name=uniprot['entry_name'].lower())
g.proteins.add(pcan)
# structures
for i, structure in enumerate(uniprot['structures']):
try:
res = structure[1]
if res == '-':
res = 0
structure, created = SignprotStructure.objects.get_or_create(
PDB_code=structure[0], resolution=res)
if created:
self.logger.info('Created structure ' +
structure.PDB_code + ' for protein ' +
p.name)
except IntegrityError:
self.logger.error('Failed creating structure ' +
structure.PDB_code + ' for protein ' +
p.name)
if g:
pcan = Protein.objects.get(
entry_name=uniprot['entry_name'].lower())
structure.origin.add(pcan)
structure.save()
def cgn_creat_gproteins(self, family, residue_numbering_scheme, accession, uniprot):
# get/create protein source
try:
source, created = ProteinSource.objects.get_or_create(name=uniprot['source'],
defaults={'name': uniprot['source']})
if created:
self.logger.info('Created protein source ' + source.name)
except IntegrityError:
source = ProteinSource.objects.get(name=uniprot['source'])
# get/create species
try:
species, created = Species.objects.get_or_create(latin_name=uniprot['species_latin_name'],
defaults={
'common_name': uniprot['species_common_name'],
})
if created:
self.logger.info('Created species ' + species.latin_name)
except IntegrityError:
species = Species.objects.get(latin_name=uniprot['species_latin_name'])
# get/create protein sequence type
# Wild-type for all sequences from source file
try:
sequence_type, created = ProteinSequenceType.objects.get_or_create(slug='wt',
defaults={
'slug': 'wt',
'name': 'Wild-type',
})
if created:
self.logger.info('Created protein sequence type Wild-type')
except:
self.logger.error('Failed creating protein sequence type Wild-type')
# create protein
p = Protein()
p.family = family
p.species = species
p.source = source
p.residue_numbering_scheme = residue_numbering_scheme
p.sequence_type = sequence_type
if accession:
p.accession = accession
p.entry_name = uniprot['entry_name'].lower()
p.name = uniprot['names'][0].split('Guanine nucleotide-binding protein ')[1]
p.sequence = uniprot['sequence']
try:
p.save()
self.logger.info('Created protein {}'.format(p.entry_name))
except:
self.logger.error('Failed creating protein {}'.format(p.entry_name))
# protein aliases
for i, alias in enumerate(uniprot['names']):
pcgn = Protein.objects.get(entry_name=uniprot['entry_name'].lower())
a = ProteinAlias()
a.protein = pcgn
a.name = alias
a.position = i
try:
a.save()
self.logger.info('Created protein alias ' + a.name + ' for protein ' + p.name)
except:
self.logger.error('Failed creating protein alias ' + a.name + ' for protein ' + p.name)
# genes
for i, gene in enumerate(uniprot['genes']):
g = False
try:
g, created = Gene.objects.get_or_create(name=gene, species=species, position=i)
if created:
self.logger.info('Created gene ' + g.name + ' for protein ' + p.name)
except IntegrityError:
g = Gene.objects.get(name=gene, species=species, position=i)
if g:
pcgn = Protein.objects.get(entry_name=uniprot['entry_name'].lower())
g.proteins.add(pcgn)
# structures
for i, structure in enumerate(uniprot['structures']):
try:
res = structure[1]
if res == '-':
res = 0
structure, created = SignprotStructure.objects.get_or_create(PDB_code=structure[0], resolution=res)
if created:
self.logger.info('Created structure ' + structure.PDB_code + ' for protein ' + p.name)
except IntegrityError:
self.logger.error('Failed creating structure ' + structure.PDB_code + ' for protein ' + p.name)
if g:
pcgn = Protein.objects.get(entry_name=uniprot['entry_name'].lower())
structure.origin.add(pcgn)
structure.save()
def create_protein(self, name, family, sequence_type,
residue_numbering_scheme, accession, uniprot):
# get/create protein source
try:
source, created = ProteinSource.objects.get_or_create(
name=uniprot['source'], defaults={'name': uniprot['source']})
if created:
self.logger.info('Created protein source ' + source.name)
except IntegrityError:
source = ProteinSource.objects.get(name=uniprot['source'])
# get/create species
try:
species, created = Species.objects.get_or_create(
latin_name=uniprot['species_latin_name'],
defaults={
'common_name': uniprot['species_common_name'],
})
if created:
self.logger.info('Created species ' + species.latin_name)
except IntegrityError:
species = Species.objects.get(
latin_name=uniprot['species_latin_name'])
# create protein
p = Protein()
p.family = family
p.species = species
p.source = source
p.residue_numbering_scheme = residue_numbering_scheme
p.sequence_type = sequence_type
if accession:
p.accession = accession
p.entry_name = uniprot['entry_name']
p.name = name
p.sequence = uniprot['sequence']
try:
p.save()
self.logger.info('Created protein {}'.format(p.entry_name))
except:
self.logger.error('Failed creating protein {}'.format(
p.entry_name))
# protein conformations
try:
ps, created = ProteinState.objects.get_or_create(
slug=settings.DEFAULT_PROTEIN_STATE,
defaults={'name': settings.DEFAULT_PROTEIN_STATE.title()})
except IntegrityError:
ps = ProteinState.objects.get(slug=settings.DEFAULT_PROTEIN_STATE)
pc = ProteinConformation.objects.create(protein=p, state=ps)
# protein aliases
for i, alias in enumerate(uniprot['names']):
a = ProteinAlias()
a.protein = p
a.name = alias
a.position = i
try:
a.save()
self.logger.info('Created protein alias ' + a.name +
' for protein ' + p.name)
except:
self.logger.error('Failed creating protein alias ' + a.name +
' for protein ' + p.name)
# genes
for i, gene in enumerate(uniprot['genes']):
g = False
try:
g, created = Gene.objects.get_or_create(name=gene,
species=species,
position=i)
if created:
self.logger.info('Created gene ' + g.name +
' for protein ' + p.name)
except IntegrityError:
g = Gene.objects.get(name=gene, species=species, position=i)
if g:
g.proteins.add(p)
def create_protein(self, name, family, sequence_type, residue_numbering_scheme, accession, uniprot):
# get/create protein source
try:
source, created = ProteinSource.objects.get_or_create(name=uniprot['source'],
defaults={'name': uniprot['source']})
if created:
self.logger.info('Created protein source ' + source.name)
except IntegrityError:
source = ProteinSource.objects.get(name=uniprot['source'])
# get/create species
try:
species, created = Species.objects.get_or_create(latin_name=uniprot['species_latin_name'],
defaults={
'common_name': uniprot['species_common_name'],
})
if created:
self.logger.info('Created species ' + species.latin_name)
except IntegrityError:
species = Species.objects.get(latin_name=uniprot['species_latin_name'])
# create protein
p = Protein()
p.family = family
p.species = species
p.source = source
p.residue_numbering_scheme = residue_numbering_scheme
p.sequence_type = sequence_type
if accession:
p.accession = accession
p.entry_name = uniprot['entry_name']
p.name = name
p.sequence = uniprot['sequence']
try:
p.save()
self.logger.info('Created protein {}'.format(p.entry_name))
except Exception as e:
self.logger.error('Failed creating protein {} {}'.format(p.entry_name, str(e)))
# protein conformations
try:
ps, created = ProteinState.objects.get_or_create(slug=settings.DEFAULT_PROTEIN_STATE,
defaults={'name': settings.DEFAULT_PROTEIN_STATE.title()})
except IntegrityError:
ps = ProteinState.objects.get(slug=settings.DEFAULT_PROTEIN_STATE)
pc = ProteinConformation.objects.create(protein=p, state=ps)
# protein aliases
for i, alias in enumerate(uniprot['names']):
a = ProteinAlias()
a.protein = p
a.name = alias
a.position = i
try:
a.save()
self.logger.info('Created protein alias ' + a.name + ' for protein ' + p.name)
except:
self.logger.error('Failed creating protein alias ' + a.name + ' for protein ' + p.name)
# genes
for i, gene in enumerate(uniprot['genes']):
g = False
try:
g, created = Gene.objects.get_or_create(name=gene, species=species, position=i)
if created:
self.logger.info('Created gene ' + g.name + ' for protein ' + p.name)
except IntegrityError:
g = Gene.objects.get(name=gene, species=species, position=i)
if g:
g.proteins.add(p)
def handle(self, *args, **options):
self.options = options
if self.options['purge']:
Residue.objects.filter(
protein_conformation__protein__entry_name__endswith='_a',
protein_conformation__protein__family__parent__parent__name=
'Alpha').delete()
ProteinConformation.objects.filter(
protein__entry_name__endswith='_a',
protein__family__parent__parent__name='Alpha').delete()
Protein.objects.filter(
entry_name__endswith='_a',
family__parent__parent__name='Alpha').delete()
SignprotStructureExtraProteins.objects.all().delete()
SignprotStructure.objects.all().delete()
if not options['only_signprot_structures']:
# Building protein and protconf objects for g protein structure in complex
scs = SignprotComplex.objects.all()
for sc in scs:
self.logger.info(
'Protein, ProteinConformation and Residue build for alpha subunit of {} is building'
.format(sc))
try:
# Alpha subunit
try:
alpha_protein = Protein.objects.get(
entry_name=sc.structure.pdb_code.index.lower() +
'_a')
except:
alpha_protein = Protein()
alpha_protein.entry_name = sc.structure.pdb_code.index.lower(
) + '_a'
alpha_protein.accession = None
alpha_protein.name = sc.structure.pdb_code.index.lower(
) + '_a'
alpha_protein.sequence = sc.protein.sequence
alpha_protein.family = sc.protein.family
alpha_protein.parent = sc.protein
alpha_protein.residue_numbering_scheme = sc.protein.residue_numbering_scheme
alpha_protein.sequence_type = ProteinSequenceType.objects.get(
slug='mod')
alpha_protein.source = ProteinSource.objects.get(
name='OTHER')
alpha_protein.species = sc.protein.species
alpha_protein.save()
try:
alpha_protconf = ProteinConformation.objects.get(
protein__entry_name=sc.structure.pdb_code.index.
lower() + '_a')
except:
alpha_protconf = ProteinConformation()
alpha_protconf.protein = alpha_protein
alpha_protconf.state = ProteinState.objects.get(
slug='active')
alpha_protconf.save()
pdbp = PDBParser(PERMISSIVE=True, QUIET=True)
s = pdbp.get_structure('struct',
StringIO(sc.structure.pdb_data.pdb))
chain = s[0][sc.alpha]
nums = []
for res in chain:
try:
res['CA']
nums.append(res.get_id()[1])
except:
pass
resis = Residue.objects.filter(
protein_conformation__protein=sc.protein)
num_i = 0
temp_seq2 = ''
pdb_num_dict = OrderedDict()
# Create first alignment based on sequence numbers
for n in nums:
if sc.structure.pdb_code.index == '6OIJ' and n < 30:
nr = n + 6
else:
nr = n
pdb_num_dict[n] = [
chain[n], resis.get(sequence_number=nr)
]
# Find mismatches
mismatches = []
for n, res in pdb_num_dict.items():
if AA[res[0].get_resname()] != res[1].amino_acid:
mismatches.append(res)
pdb_lines = sc.structure.pdb_data.pdb.split('\n')
seqadv = []
for l in pdb_lines:
if l.startswith('SEQADV'):
seqadv.append(l)
mutations, shifted_mutations = OrderedDict(), OrderedDict()
# Search for annotated engineered mutations in pdb SEQADV
for s in seqadv:
line_search = re.search(
'SEQADV\s{1}[A-Z\s\d]{4}\s{1}([A-Z]{3})\s{1}([A-Z]{1})\s+(\d+)[\s\S\d]{5}([\s\S\d]{12})([A-Z]{3})\s+(\d+)(\s\S+)',
s)
if line_search != None:
if line_search.group(2) == sc.alpha:
if line_search.group(
4).strip() == sc.protein.accession:
if line_search.group(
3) == line_search.group(6):
mutations[int(
line_search.group(3))] = [
line_search.group(1),
line_search.group(5)
]
else:
shifted_mutations[int(
line_search.group(3))] = [
line_search.group(1),
line_search.group(5),
int(line_search.group(6))
]
else:
# Exception for 6G79
if line_search.group(
3
) != line_search.group(
6
) and 'CONFLICT' in line_search.group(7):
mutations[int(
line_search.group(3))] = [
line_search.group(1),
line_search.group(5)
]
# Exception for 5G53
if line_search.group(
4).strip() != sc.protein.accession:
mutations[int(
line_search.group(3))] = [
line_search.group(1),
line_search.group(5)
]
remaining_mismatches = []
# Check and clear mismatches that are registered in pdb SEQADV as engineered mutation
for m in mismatches:
num = m[0].get_id()[1]
if num in mutations:
if m[0].get_resname() != mutations[num][0] and m[
1].amino_acid != AA[mutations[num][1]]:
remaining_mismatches.append(m)
elif num in shifted_mutations:
remaining_mismatches.append(m)
else:
remaining_mismatches.append(m)
### sanity check
# print(sc)
# print(mutations)
# print(shifted_mutations)
# print(mismatches)
# print('======')
# print(remaining_mismatches)
# pprint.pprint(pdb_num_dict)
# Mismatches remained possibly to seqnumber shift, making pairwise alignment to try and fix alignment
if len(remaining_mismatches
) > 0 and sc.structure.pdb_code.index not in [
'6OIJ', '6OY9', '6OYA', '6LPB', '6WHA'
]:
ppb = PPBuilder()
seq = ''
for pp in ppb.build_peptides(chain, aa_only=False):
seq += str(pp.get_sequence())
pw2 = pairwise2.align.localms(sc.protein.sequence, seq,
2, -1, -.5, -.1)
ref_seq, temp_seq = str(pw2[0][0]), str(pw2[0][1])
wt_pdb_dict = OrderedDict()
pdb_wt_dict = OrderedDict()
j, k = 0, 0
for i, ref, temp in zip(range(0, len(ref_seq)),
ref_seq, temp_seq):
# print(i, ref, temp) # alignment check
if ref != '-' and temp != '-':
wt_pdb_dict[resis[j]] = pdb_num_dict[nums[k]]
pdb_wt_dict[pdb_num_dict[nums[k]]
[0]] = resis[j]
j += 1
k += 1
elif ref == '-':
wt_pdb_dict[i] = pdb_num_dict[nums[k]]
pdb_wt_dict[pdb_num_dict[nums[k]][0]] = i
k += 1
elif temp == '-':
wt_pdb_dict[resis[j]] = i
pdb_wt_dict[i] = resis[j]
j += 1
for i, r in enumerate(remaining_mismatches):
# Adjust for shifted residue when residue is a match
if r[0].get_id()[1] - remaining_mismatches[
i - 1][0].get_id()[1] > 1:
pdb_num_dict[r[0].get_id()[1] -
1][1] = pdb_wt_dict[chain[
r[0].get_id()[1] - 1]]
# Adjust for shifted residue when residue is mutated and it's logged in SEQADV
if r[0].get_id()[1] in shifted_mutations:
pdb_num_dict[r[0].get_id()[1]][1] = resis.get(
sequence_number=shifted_mutations[
r[0].get_id()[1]][2])
# Adjust for shift
else:
pdb_num_dict[r[0].get_id()
[1]][1] = pdb_wt_dict[r[0]]
# Custom alignment fix for 6WHA mini-Gq/Gi2/Gs chimera
# elif sc.structure.pdb_code.index=='6WHA':
# ref_seq = 'MTLESIMACCLSEEAKEARRINDEIERQLRRDKRDARRELKLLLLGTGESGKSTFIKQMRIIHGSGYSDEDKRGFTKLVYQNIFTAMQAMIRAMDTLKIPYKYEHNKAHAQLVREVDVEKVSAFENPYVDAIKSLWNDPGIQECYDRRREYQLSDSTKYYLNDLDRVADPAYLPTQQDVLRVRVPTTGIIEYPFDLQSVIFRMVDVGGQRSERRKWIHCFENVTSIMFLVALSEYDQVLVESDNENRMEESKALFRTIITYPWFQNSSVILFLNKKDLLEEKIMY--SHLVDYFPEYDGP----QRDAQAAREFILKMFVDL---NPDSDKIIYSHFTCATDTENIRFVFAAVKDTILQLNLKEYNLV'
# temp_seq = '----------VSAEDKAAAERSKMIDKNLREDGEKARRTLRLLLLGADNSGKSTIVK----------------------------------------------------------------------------------------------------------------------------------GIFETKFQVDKVNFHMFDVG-----RRKWIQCFNDVTAIIFVVDSSDYNR----------LQEALNDFKSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFARYTTPDPRVTRAKY-FIRKEFVDISTASGDGRHICYPHFTC-VDTENARRIFNDCKDIILQMNLREYNLV'
# for i, ref, temp in zip(range(0,len(ref_seq)), ref_seq, temp_seq):
# print(i, ref, temp)
# pprint.pprint(pdb_num_dict)
bulked_residues = []
for key, val in pdb_num_dict.items():
# print(key, val) # sanity check
if not isinstance(val[1], int):
res_obj = Residue()
res_obj.sequence_number = val[0].get_id()[1]
res_obj.amino_acid = AA[val[0].get_resname()]
res_obj.display_generic_number = val[
1].display_generic_number
res_obj.generic_number = val[1].generic_number
res_obj.protein_conformation = alpha_protconf
res_obj.protein_segment = val[1].protein_segment
bulked_residues.append(res_obj)
else:
self.logger.info(
'Skipped {} as no annotation was present, while building for alpha subunit of {}'
.format(val[1], sc))
Residue.objects.bulk_create(bulked_residues)
self.logger.info(
'Protein, ProteinConformation and Residue build for alpha subunit of {} is finished'
.format(sc))
except Exception as msg:
#print('Protein, ProteinConformation and Residue build for alpha subunit of {} has failed'.format(sc))
#print(msg)
#print(traceback.format_exc())
#exit(0)
self.logger.info(
'Protein, ProteinConformation and Residue build for alpha subunit of {} has failed'
.format(sc))
### Build SignprotStructure objects from non-complex signprots
g_prot_alphas = Protein.objects.filter(
family__slug__startswith='100_001',
accession__isnull=False) #.filter(entry_name='gnai1_human')
complex_structures = SignprotComplex.objects.all().values_list(
'structure__pdb_code__index', flat=True)
for a in g_prot_alphas:
pdb_list = get_pdb_ids(a.accession)
for pdb in pdb_list:
if pdb not in complex_structures:
try:
data = self.fetch_gprot_data(pdb, a)
if data:
self.build_g_prot_struct(a, pdb, data)
except Exception as msg:
self.logger.error(
'SignprotStructure of {} {} failed\n{}: {}'.format(
a.entry_name, pdb, type(msg), msg))
def handle(self, *args, **options):
startTime = datetime.datetime.now()
self.options = options
if self.options["purge"]:
Residue.objects.filter(
protein_conformation__protein__entry_name__endswith="_a",
protein_conformation__protein__family__parent__parent__name=
"Alpha").delete()
ProteinConformation.objects.filter(
protein__entry_name__endswith="_a",
protein__family__parent__parent__name="Alpha").delete()
Protein.objects.filter(
entry_name__endswith="_a",
family__parent__parent__name="Alpha").delete()
SignprotStructureExtraProteins.objects.all().delete()
SignprotStructure.objects.all().delete()
if not options["only_signprot_structures"]:
# Building protein and protconf objects for g protein structure in complex
if options["s"]:
scs = SignprotComplex.objects.filter(
structure__pdb_code__index__in=[
i.upper() for i in options["s"]
])
else:
scs = SignprotComplex.objects.all()
for sc in scs:
self.logger.info(
"Protein, ProteinConformation and Residue build for alpha subunit of {} is building"
.format(sc))
try:
# Alpha subunit
try:
alpha_protein = Protein.objects.get(
entry_name=sc.structure.pdb_code.index.lower() +
"_a")
except:
alpha_protein = Protein()
alpha_protein.entry_name = sc.structure.pdb_code.index.lower(
) + "_a"
alpha_protein.accession = None
alpha_protein.name = sc.structure.pdb_code.index.lower(
) + "_a"
alpha_protein.sequence = sc.protein.sequence
alpha_protein.family = sc.protein.family
alpha_protein.parent = sc.protein
alpha_protein.residue_numbering_scheme = sc.protein.residue_numbering_scheme
alpha_protein.sequence_type = ProteinSequenceType.objects.get(
slug="mod")
alpha_protein.source = ProteinSource.objects.get(
name="OTHER")
alpha_protein.species = sc.protein.species
alpha_protein.save()
try:
alpha_protconf = ProteinConformation.objects.get(
protein__entry_name=sc.structure.pdb_code.index.
lower() + "_a")
except:
alpha_protconf = ProteinConformation()
alpha_protconf.protein = alpha_protein
alpha_protconf.state = ProteinState.objects.get(
slug="active")
alpha_protconf.save()
pdbp = PDBParser(PERMISSIVE=True, QUIET=True)
s = pdbp.get_structure("struct",
StringIO(sc.structure.pdb_data.pdb))
chain = s[0][sc.alpha]
nums = []
for res in chain:
if "CA" in res and res.id[0] == " ":
nums.append(res.get_id()[1])
resis = Residue.objects.filter(
protein_conformation__protein=sc.protein)
num_i = 0
temp_seq2 = ""
pdb_num_dict = OrderedDict()
# Create first alignment based on sequence numbers
for n in nums:
if sc.structure.pdb_code.index == "6OIJ" and n < 30:
nr = n + 6
else:
nr = n
pdb_num_dict[n] = [
chain[n], resis.get(sequence_number=nr)
]
# Find mismatches
mismatches = []
for n, res in pdb_num_dict.items():
if AA[res[0].get_resname()] != res[1].amino_acid:
mismatches.append(res)
pdb_lines = sc.structure.pdb_data.pdb.split("\n")
seqadv = []
for l in pdb_lines:
if l.startswith("SEQADV"):
seqadv.append(l)
mutations, shifted_mutations = OrderedDict(), OrderedDict()
# Search for annotated engineered mutations in pdb SEQADV
for s in seqadv:
line_search = re.search(
"SEQADV\s{1}[A-Z\s\d]{4}\s{1}([A-Z]{3})\s{1}([A-Z]{1})\s+(\d+)[\s\S\d]{5}([\s\S\d]{12})([A-Z]{3})\s+(\d+)(\s\S+)",
s)
if line_search != None:
if line_search.group(2) == sc.alpha:
if line_search.group(
4).strip() == sc.protein.accession:
if line_search.group(
3) == line_search.group(6):
mutations[int(
line_search.group(3))] = [
line_search.group(1),
line_search.group(5)
]
else:
shifted_mutations[int(
line_search.group(3))] = [
line_search.group(1),
line_search.group(5),
int(line_search.group(6))
]
else:
# Exception for 6G79
if line_search.group(
3
) != line_search.group(
6
) and "CONFLICT" in line_search.group(7):
mutations[int(
line_search.group(3))] = [
line_search.group(1),
line_search.group(5)
]
# Exception for 5G53
if line_search.group(
4).strip() != sc.protein.accession:
mutations[int(
line_search.group(3))] = [
line_search.group(1),
line_search.group(5)
]
remaining_mismatches = []
# Check and clear mismatches that are registered in pdb SEQADV as engineered mutation
for m in mismatches:
num = m[0].get_id()[1]
if num in mutations:
if m[0].get_resname() != mutations[num][0] and m[
1].amino_acid != AA[mutations[num][1]]:
remaining_mismatches.append(m)
elif num in shifted_mutations:
remaining_mismatches.append(m)
else:
remaining_mismatches.append(m)
if options["debug"]:
print(sc)
print(mutations)
print(shifted_mutations)
print(mismatches)
print("======")
print(remaining_mismatches)
pprint.pprint(pdb_num_dict)
no_seqnum_shift = [
'6OY9', '6OYA', '6LPB', '6WHA', '7D77', '6XOX', '7L1U',
'7L1V'
]
# Check if HN is mutated to GNAI1 for the scFv16 stabilizer
if sc.protein.entry_name != 'gnai1_human' and len(
remaining_mismatches) > 0:
target_HN = resis.filter(protein_segment__slug='HN')
gnai1_HN = Residue.objects.filter(
protein_conformation__protein__entry_name=
'gnai1_human',
protein_segment__slug='HN')
pdb_HN_seq = ''
for num, val in pdb_num_dict.items():
if num <= target_HN.reverse()[0].sequence_number:
pdb_HN_seq += Polypeptide.three_to_one(
val[0].get_resname())
if options['debug']:
print('Checking if HN is gnai1_human')
print(pdb_HN_seq)
print(''.join(
gnai1_HN.values_list('amino_acid', flat=True)))
gnai1_HN_seq = ''.join(
gnai1_HN.values_list('amino_acid', flat=True))
pw2 = pairwise2.align.localms(gnai1_HN_seq, pdb_HN_seq,
3, -4, -3, -1)
ref_seq, temp_seq = str(pw2[0][0]), str(pw2[0][1])
length, match = 0, 0
for r, t in zip(ref_seq, temp_seq):
if options['debug']:
print(r, t)
if t != '-':
if r == t:
match += 1
length += 1
identity = match / length * 100
if options['debug']:
print(identity)
if identity > 85:
if sc.structure.pdb_code.index not in ['7DFL']:
no_seqnum_shift.append(
sc.structure.pdb_code.index)
if options['debug']:
print(
'INFO: HN has {}% with gnai1_human HN, skipping seqnum shift correction'
.format(round(identity)))
# Mismatches remained possibly to seqnumber shift, making pairwise alignment to try and fix alignment
if len(
remaining_mismatches
) > 0 and sc.structure.pdb_code.index not in no_seqnum_shift:
ppb = PPBuilder()
seq = ""
for pp in ppb.build_peptides(chain, aa_only=False):
seq += str(pp.get_sequence())
if sc.structure.pdb_code.index in [
'7JVQ', '7L1U', '7L1V'
]:
pw2 = pairwise2.align.localms(
sc.protein.sequence, seq, 3, -4, -3, -1)
else:
pw2 = pairwise2.align.localms(
sc.protein.sequence, seq, 2, -1, -.5, -.1)
ref_seq, temp_seq = str(pw2[0][0]), str(pw2[0][1])
# Custom fix for A->G mutation at pos 18
if sc.structure.pdb_code.index == '7JJO':
ref_seq = ref_seq[:18] + ref_seq[19:]
temp_seq = temp_seq[:17] + temp_seq[18:]
# Custom alignment fixes
elif sc.structure.pdb_code.index == '7DFL':
ref_seq = 'MTLESIMACCLSEEAKEARRINDEIERQLRRDKRDARRELKLLLLGTGESGKSTFIKQMRIIHGSGYSDEDKRGFTKLVYQNIFTAMQAMIRAMDTLKIPYKYEHNKAHAQLVREVDVEKVSAFENPYVDAIKSLWNDPGIQECYDRRREYQLSDSTKYYLNDLDRVADPAYLPTQQDVLRVRVPTTGIIEYPFDLQSVIFRMVDVGGQRSERRKWIHCFENVTSIMFLVALSEYDQVLVESDNENRMEESKALFRTIITYPWFQNSSVILFLNKKDLLEEKIMYSHLVDYFPEYDGPQRDAQAAREFILKMFVDLNPDSDKIIYSHFTCATDTENIRFVFAAVKDTILQLNLKEYNLV'
temp_seq = '--------CTLSAEDKAAVERSKMIDRNLREDGEKARRELKLLLLGTGESGKSTFIKQMRIIHG--------------------------------------------------------------------------------------------------------------------------TGIIEYPFDLQSVIFRMVDVGGQRSERRKWIHCFENVTSIMFLVALSEYDQV----DNENRMEESKALFRTIITYPWFQNSSVILFLNKKDLLEEKIMYSHLVDYFPEYDGPQRDAQAAREFILKMFVDLNPDSDKILYSHFTCATDTENIRFVFAAVKDTILQLNLKEYNLV'
elif sc.structure.pdb_code.index == '7JOZ':
temp_seq = temp_seq[:67] + (
'-' * 14) + 'FNGDS' + temp_seq[86:]
elif sc.structure.pdb_code.index == '7AUE':
ref_seq = ref_seq[:31].replace('-',
'') + ref_seq[31:]
temp_seq = (
9 *
'-') + temp_seq[2:5] + temp_seq[5:54].replace(
'-', '') + temp_seq[54:]
wt_pdb_dict = OrderedDict()
pdb_wt_dict = OrderedDict()
j, k = 0, 0
for i, ref, temp in zip(range(0, len(ref_seq)),
ref_seq, temp_seq):
if options["debug"]:
print(i, ref, temp) # alignment check
if ref != "-" and temp != "-":
wt_pdb_dict[resis[j]] = pdb_num_dict[nums[k]]
pdb_wt_dict[pdb_num_dict[nums[k]]
[0]] = resis[j]
j += 1
k += 1
elif ref == "-":
wt_pdb_dict[i] = pdb_num_dict[nums[k]]
pdb_wt_dict[pdb_num_dict[nums[k]][0]] = i
k += 1
elif temp == "-":
wt_pdb_dict[resis[j]] = i
pdb_wt_dict[i] = resis[j]
j += 1
# Custom fix for 7JJO isoform difference
if sc.structure.pdb_code.index in [
'7JJO', '7JOZ', '7AUE'
]:
pdb_num_dict = OrderedDict()
for wt_res, st_res in wt_pdb_dict.items():
if type(st_res) == type([]):
pdb_num_dict[wt_res.sequence_number] = [
st_res[0], wt_res
]
else:
for i, r in enumerate(remaining_mismatches):
# Adjust for shifted residue when residue is a match
if r[0].get_id()[1] - remaining_mismatches[
i - 1][0].get_id()[1] > 1:
pdb_num_dict[r[0].get_id()[1] -
1][1] = pdb_wt_dict[chain[
r[0].get_id()[1] - 1]]
# Adjust for shifted residue when residue is mutated and it's logged in SEQADV
if r[0].get_id()[1] in shifted_mutations:
pdb_num_dict[
r[0].get_id()[1]][1] = resis.get(
sequence_number=shifted_mutations[
r[0].get_id()[1]][2])
# Adjust for shift
else:
pdb_num_dict[r[0].get_id()
[1]][1] = pdb_wt_dict[r[0]]
if sc.structure.pdb_code.index == '7JVQ':
pdb_num_dict[198][1] = Residue.objects.get(
protein_conformation__protein=sc.protein,
sequence_number=346)
pdb_num_dict[235][1] = Residue.objects.get(
protein_conformation__protein=sc.protein,
sequence_number=383)
elif sc.structure.pdb_code.index == '6PB0':
pdb_num_dict[205][1] = Residue.objects.get(
protein_conformation__protein=sc.protein,
sequence_number=205)
### Custom alignment fix for 6WHA mini-Gq/Gi2/Gs chimera
elif sc.structure.pdb_code.index == "6WHA":
ref_seq = "MTLESIMACCLSEEAKEARRINDEIERQLRRDKRDARRELKLLLLGTGESGKSTFIKQMRIIHGSGYSDEDKRGFTKLVYQNIFTAMQAMIRAMDTLKIPYKYEHNKAHAQLVREVDVEKVSAFENPYVDAIKSLWNDPGIQECYDRRREYQLSDSTKYYLNDLDRVADPAYLPTQQDVLRVRVPTTGIIEYPFDLQSVIFRMVDVGGQRSERRKWIHCFENVTSIMFLVALSEYDQVLVESDNENRMEESKALFRTIITYPWFQNSSVILFLNKKDLLEEKIM--YSHLVDYFPEYDGP----QRDAQAAREFILKMFVDL---NPDSDKIIYSHFTCATDTENIRFVFAAVKDTILQLNLKEYNLV"
temp_seq = "----------VSAEDKAAAERSKMIDKNLREDGEKARRTLRLLLLGADNSGKSTIVK----------------------------------------------------------------------------------------------------------------------------------GIFETKFQVDKVNFHMFDVG-----RRKWIQCFNDVTAIIFVVDSSDYNR----------LQEALNDFKSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFARYTTPDPRVTRAKY-FIRKEFVDISTASGDGRHICYPHFTC-VDTENARRIFNDCKDIILQMNLREYNLV"
pdb_num_dict = OrderedDict()
temp_resis = [res for res in chain]
temp_i = 0
mapped_cgns = []
for i, aa in enumerate(temp_seq):
if aa != "-":
ref_split_on_gaps = ref_seq[:i + 1].split("-")
ref_seqnum = i - (len(ref_split_on_gaps) -
1) + 1
res = resis.get(sequence_number=ref_seqnum)
if res.display_generic_number.label in mapped_cgns:
next_presumed_cgn = self.get_next_presumed_cgn(
res)
if next_presumed_cgn:
res = next_presumed_cgn
while res and res.display_generic_number.label in mapped_cgns:
res = self.get_next_presumed_cgn(
res)
else:
print(
"Error: {} CGN does not exist. Incorrect mapping of {} in {}"
.format(next_presumed_cgn,
chain[nums[temp_i]],
sc.structure))
mapped_cgns.append(
res.display_generic_number.label)
pdb_num_dict[nums[temp_i]] = [
chain[nums[temp_i]], res
]
temp_i += 1
bulked_rotamers = []
for key, val in pdb_num_dict.items():
# print(key, val) # sanity check
if not isinstance(val[1], int):
res_obj = Residue()
res_obj.sequence_number = val[0].get_id()[1]
res_obj.amino_acid = AA[val[0].get_resname()]
res_obj.display_generic_number = val[
1].display_generic_number
res_obj.generic_number = val[1].generic_number
res_obj.protein_conformation = alpha_protconf
res_obj.protein_segment = val[1].protein_segment
res_obj.save()
rot = self.create_structure_rotamer(
val[0], res_obj, sc.structure)
bulked_rotamers.append(rot)
else:
self.logger.info(
"Skipped {} as no annotation was present, while building for alpha subunit of {}"
.format(val[1], sc))
if options["debug"]:
pprint.pprint(pdb_num_dict)
Rotamer.objects.bulk_create(bulked_rotamers)
self.logger.info(
"Protein, ProteinConformation and Residue build for alpha subunit of {} is finished"
.format(sc))
except Exception as msg:
if options["debug"]:
print("Error: ", sc, msg)
self.logger.info(
"Protein, ProteinConformation and Residue build for alpha subunit of {} has failed"
.format(sc))
if not options["s"]:
### Build SignprotStructure objects from non-complex signprots
g_prot_alphas = Protein.objects.filter(
family__slug__startswith="100_001",
accession__isnull=False) #.filter(entry_name="gnai1_human")
complex_structures = SignprotComplex.objects.all().values_list(
"structure__pdb_code__index", flat=True)
for a in g_prot_alphas:
pdb_list = get_pdb_ids(a.accession)
for pdb in pdb_list:
if pdb not in complex_structures:
try:
data = self.fetch_gprot_data(pdb, a)
if data:
self.build_g_prot_struct(a, pdb, data)
except Exception as msg:
self.logger.error(
"SignprotStructure of {} {} failed\n{}: {}".
format(a.entry_name, pdb, type(msg), msg))
if options["debug"]:
print(datetime.datetime.now() - startTime)
