def fetch_pdb(pdbid):
"""Get the newest entry from the RCSB server for the given PDB ID. Exits with '1' if PDB ID is invalid."""
pdbid = pdbid.lower()
logger.info(f'checking status of PDB-ID {pdbid}')
# @todo re-implement state check with ew RCSB API, see https://www.rcsb.org/news?year=2020&article=5eb18ccfd62245129947212a&feature=true
# state, current_entry = check_pdb_status(pdbid) # Get state and current PDB ID
#
# if state == 'OBSOLETE':
# logger.info(f'entry is obsolete, getting {current_entry} instead')
# elif state == 'CURRENT':
# logger.info('entry is up-to-date')
# elif state == 'UNKNOWN':
# logger.error('invalid PDB-ID (entry does not exist on PDB server)')
# sys.exit(1)
logger.info('downloading file from PDB')
# get URL for current entry
# @todo needs update to react properly on response codes of RCSB servers
pdburl = f'http://www.rcsb.org/pdb/files/{pdbid}.pdb'
try:
pdbfile = urlopen(pdburl).read().decode()
# If no PDB file is available, a text is now shown with "We're sorry, but ..."
# Could previously be distinguished by an HTTP error
if 'sorry' in pdbfile:
logger.error('no file in PDB format available from wwPDB for the given PDB ID.')
sys.exit(1)
except HTTPError:
logger.error('no file in PDB format available from wwPDB for the given PDB ID')
sys.exit(1)
return [pdbfile, pdbid]
def run_analysis(inputstructs, inputpdbids):
"""Main function. Calls functions for processing, report generation and visualization."""
pdbid, pdbpath = None, None
# @todo For multiprocessing, implement better stacktracing for errors
# Print title and version
logger.info(f'Protein-Ligand Interaction Profiler (PLIP) {__version__}')
logger.info(f'brought to you by: {config.__maintainer__}')
logger.info(f'please cite: https://www.doi.org/10.1093/nar/gkv315')
output_prefix = config.OUTPUTFILENAME
if inputstructs is not None: # Process PDB file(s)
num_structures = len(inputstructs)
inputstructs = remove_duplicates(inputstructs)
read_from_stdin = False
for inputstruct in inputstructs:
if inputstruct == '-':
inputstruct = sys.stdin.read()
read_from_stdin = True
if config.RAWSTRING:
if sys.version_info < (3, ):
inputstruct = bytes(inputstruct).decode(
'unicode_escape')
else:
inputstruct = bytes(inputstruct,
'utf8').decode('unicode_escape')
else:
if os.path.getsize(inputstruct) == 0:
logger.error('empty PDB file')
sys.exit(1)
if num_structures > 1:
basename = inputstruct.split('.')[-2].split('/')[-1]
config.OUTPATH = '/'.join([config.BASEPATH, basename])
output_prefix = 'report'
process_pdb(inputstruct,
config.OUTPATH,
as_string=read_from_stdin,
outputprefix=output_prefix)
else: # Try to fetch the current PDB structure(s) directly from the RCBS server
num_pdbids = len(inputpdbids)
inputpdbids = remove_duplicates(inputpdbids)
for inputpdbid in inputpdbids:
pdbpath, pdbid = download_structure(inputpdbid)
if num_pdbids > 1:
config.OUTPATH = '/'.join(
[config.BASEPATH, pdbid[1:3].upper(),
pdbid.upper()])
output_prefix = 'report'
process_pdb(pdbpath, config.OUTPATH, outputprefix=output_prefix)
if (pdbid is not None
or inputstructs is not None) and config.BASEPATH is not None:
if config.BASEPATH in ['.', './']:
logger.info(
'finished analysis, find the result files in the working directory'
)
else:
logger.info(
f'finished analysis, find the result files in {config.BASEPATH}'
)
def remove_duplicates(slist):
"""Checks input lists for duplicates and returns
a list with unique entries"""
unique = list(set(slist))
difference = len(slist) - len(unique)
if difference == 1:
logger.info('removed one duplicate entry from input list')
if difference > 1:
logger.info(f'Removed {difference} duplicate entries from input list')
return unique
def process_pdb(pdbfile, outpath, as_string=False, outputprefix='report'):
"""Analysis of a single PDB file. Can generate textual reports XML, PyMOL session files and images as output."""
if not as_string:
pdb_file_name = pdbfile.split('/')[-1]
startmessage = f'starting analysis of {pdb_file_name}'
else:
startmessage = 'starting analysis from STDIN'
logger.info(startmessage)
mol = PDBComplex()
mol.output_path = outpath
mol.load_pdb(pdbfile, as_string=as_string)
# @todo Offers possibility for filter function from command line (by ligand chain, position, hetid)
for ligand in mol.ligands:
mol.characterize_complex(ligand)
create_folder_if_not_exists(outpath)
# Generate the report files
streport = StructureReport(mol, outputprefix=outputprefix)
config.MAXTHREADS = min(config.MAXTHREADS, len(mol.interaction_sets))
######################################
# PyMOL Visualization (parallelized) #
######################################
if config.PYMOL or config.PICS:
from plip.visualization.visualize import visualize_in_pymol
complexes = [
VisualizerData(mol, site) for site in sorted(mol.interaction_sets)
if not len(mol.interaction_sets[site].interacting_res) == 0
]
if config.MAXTHREADS > 1:
logger.info(
f'generating visualizations in parallel on {config.MAXTHREADS} cores'
)
parfn = parallel_fn(visualize_in_pymol)
parfn(complexes, processes=config.MAXTHREADS)
else:
[visualize_in_pymol(plcomplex) for plcomplex in complexes]
if config.XML: # Generate report in xml format
streport.write_xml(as_string=config.STDOUT)
if config.TXT: # Generate report in txt (rst) format
streport.write_txt(as_string=config.STDOUT)
def hbonds(acceptors, donor_pairs, protisdon, typ):
"""Detection of hydrogen bonds between sets of acceptors and donor pairs.
Definition: All pairs of hydrogen bond acceptor and donors with
donor hydrogens and acceptor showing a distance within HBOND DIST MIN and HBOND DIST MAX
and donor angles above HBOND_DON_ANGLE_MIN
"""
data = namedtuple('hbond', 'a a_orig_idx d d_orig_idx h distance_ah distance_ad angle type protisdon resnr '
'restype reschain resnr_l restype_l reschain_l sidechain atype dtype')
pairings = []
# DEBUG
if protisdon:
logger.info(f'Ligand has {len(acceptors)} acceptors')
logger.info(f'Prot has {len(donor_pairs)} donor pairs of type {typ}')
else:
logger.info(f'Prot has {len(acceptors)} acceptors')
logger.info(f'Lig has {len(donor_pairs)} donor pairs of type {typ}')
for acc, don in itertools.product(acceptors, donor_pairs):
#if not typ == 'strong':
#continue # keep only the strong hydrogen bonds (default plip version)
# Regular (strong) hydrogen bonds
dist_ah = euclidean3d(acc.a.coords, don.h.coords) # acceptor to H dist
dist_ad = euclidean3d(acc.a.coords, don.d.coords) # acceptor to donor dist
if not config.MIN_DIST < dist_ad < config.HBOND_DIST_MAX:
continue
vec1, vec2 = vector(don.h.coords, don.d.coords), vector(don.h.coords, acc.a.coords)
v = vecangle(vec1, vec2)
if not v > config.HBOND_DON_ANGLE_MIN:
continue
protatom = don.d.OBAtom if protisdon else acc.a.OBAtom
ligatom = don.d.OBAtom if not protisdon else acc.a.OBAtom
is_sidechain_hbond = protatom.GetResidue().GetAtomProperty(protatom, 8) # Check if sidechain atom
resnr = whichresnumber(don.d) if protisdon else whichresnumber(acc.a)
resnr_l = whichresnumber(acc.a_orig_atom) if protisdon else whichresnumber(don.d_orig_atom)
restype = whichrestype(don.d) if protisdon else whichrestype(acc.a)
restype_l = whichrestype(acc.a_orig_atom) if protisdon else whichrestype(don.d_orig_atom)
reschain = whichchain(don.d) if protisdon else whichchain(acc.a)
rechain_l = whichchain(acc.a_orig_atom) if protisdon else whichchain(don.d_orig_atom)
# Next line prevents H-Bonds within amino acids in intermolecular interactions
if config.INTRA is not None and whichresnumber(don.d) == whichresnumber(acc.a):
continue
# Next line prevents backbone-backbone H-Bonds
if config.INTRA is not None and protatom.GetResidue().GetAtomProperty(protatom,
8) and ligatom.GetResidue().GetAtomProperty(
ligatom, 8):
continue
contact = data(a=acc.a, a_orig_idx=acc.a_orig_idx, d=don.d, d_orig_idx=don.d_orig_idx, h=don.h,
distance_ah=dist_ah, distance_ad=dist_ad, angle=v, type=typ, protisdon=protisdon,
resnr=resnr, restype=restype, reschain=reschain, resnr_l=resnr_l,
restype_l=restype_l, reschain_l=rechain_l, sidechain=is_sidechain_hbond,
atype=acc.a.type, dtype=don.d.type)
pairings.append(contact)
return filter_contacts(pairings)
def download_structure(inputpdbid):
"""Given a PDB ID, downloads the corresponding PDB structure.
Checks for validity of ID and handles error while downloading.
Returns the path of the downloaded file."""
try:
if len(inputpdbid) != 4 or extract_pdbid(inputpdbid.lower()) == 'UnknownProtein':
logger.error(f'invalid PDB-ID (wrong format): {inputpdbid}')
sys.exit(1)
pdbfile, pdbid = fetch_pdb(inputpdbid.lower())
pdbpath = tilde_expansion('%s/%s.pdb' % (config.BASEPATH.rstrip('/'), pdbid))
create_folder_if_not_exists(config.BASEPATH)
with open(pdbpath, 'w') as g:
g.write(pdbfile)
logger.info(f'file downloaded as {pdbpath}')
return pdbpath, pdbid
except ValueError: # Invalid PDB ID, cannot fetch from RCBS server
logger.error(f'PDB-ID does not exist: {inputpdbid}')
sys.exit(1)
def metal_complexation(metals, metal_binding_lig, metal_binding_bs):
"""Find all metal complexes between metals and appropriate groups in both protein and ligand, as well as water"""
data = namedtuple(
'metal_complex',
'metal metal_orig_idx metal_type target target_orig_idx target_type '
'coordination_num distance resnr restype '
'reschain restype_l reschain_l resnr_l location rms, geometry num_partners complexnum'
)
pairings_dict = {}
pairings = []
# #@todo Refactor
metal_to_id = {}
metal_to_orig_atom = {}
for metal, target in itertools.product(
metals, metal_binding_lig + metal_binding_bs):
distance = euclidean3d(metal.m.coords, target.atom.coords)
if not distance < config.METAL_DIST_MAX:
continue
if metal.m not in pairings_dict:
pairings_dict[metal.m] = [
(target, distance),
]
metal_to_id[metal.m] = metal.m_orig_idx
metal_to_orig_atom[metal.m] = metal.orig_m
else:
pairings_dict[metal.m].append((target, distance))
for cnum, metal in enumerate(pairings_dict):
rms = 0.0
excluded = []
# cnum +1 being the complex number
contact_pairs = pairings_dict[metal]
num_targets = len(contact_pairs)
vectors_dict = defaultdict(list)
for contact_pair in contact_pairs:
target, distance = contact_pair
vectors_dict[target.atom.idx].append(
vector(metal.coords, target.atom.coords))
# Listing of coordination numbers and their geometries
configs = {
2: [
'linear',
],
3: ['trigonal.planar', 'trigonal.pyramidal'],
4: ['tetrahedral', 'square.planar'],
5: ['trigonal.bipyramidal', 'square.pyramidal'],
6: [
'octahedral',
]
}
# Angle signatures for each geometry (as seen from each target atom)
ideal_angles = {
'linear': [[180.0]] * 2,
'trigonal.planar': [[120.0, 120.0]] * 3,
'trigonal.pyramidal': [[109.5, 109.5]] * 3,
'tetrahedral': [[109.5, 109.5, 109.5, 109.5]] * 4,
'square.planar': [[90.0, 90.0, 90.0, 90.0]] * 4,
'trigonal.bipyramidal':
[[120.0, 120.0, 90.0, 90.0]] * 3 + [[90.0, 90.0, 90.0, 180.0]] * 2,
'square.pyramidal':
[[90.0, 90.0, 90.0, 180.0]] * 4 + [[90.0, 90.0, 90.0, 90.0]],
'octahedral': [[90.0, 90.0, 90.0, 90.0, 180.0]] * 6
}
angles_dict = {}
for target in vectors_dict:
cur_vector = vectors_dict[target]
other_vectors = []
for t in vectors_dict:
if not t == target:
[other_vectors.append(x) for x in vectors_dict[t]]
angles = [
vecangle(pair[0], pair[1])
for pair in itertools.product(cur_vector, other_vectors)
]
angles_dict[target] = angles
all_total = [] # Record fit information for each geometry tested
gdata = namedtuple(
'gdata',
'geometry rms coordination excluded diff_targets') # Geometry Data
# Can't specify geometry with only one target
if num_targets == 1:
final_geom = 'NA'
final_coo = 1
excluded = []
rms = 0.0
else:
for coo in sorted(
configs,
reverse=True): # Start with highest coordination number
geometries = configs[coo]
for geometry in geometries:
signature = ideal_angles[
geometry] # Set of ideal angles for geometry, from each perspective
geometry_total = 0
geometry_scores = [
] # All scores for one geometry (from all subsignatures)
used_up_targets = [
] # Use each target just once for a subsignature
not_used = []
coo_diff = num_targets - coo # How many more observed targets are there?
# Find best match for each subsignature
for subsignature in signature: # Ideal angles from one perspective
best_target = None # There's one best-matching target for each subsignature
best_target_score = 999
for k, target in enumerate(angles_dict):
if target not in used_up_targets:
observed_angles = angles_dict[
target] # Observed angles from perspective of one target
single_target_scores = []
used_up_observed_angles = []
for i, ideal_angle in enumerate(subsignature):
# For each angle in the signature, find the best-matching observed angle
best_match = None
best_match_diff = 999
for j, observed_angle in enumerate(
observed_angles):
if j not in used_up_observed_angles:
diff = abs(ideal_angle -
observed_angle)
if diff < best_match_diff:
best_match_diff = diff
best_match = j
if best_match is not None:
used_up_observed_angles.append(
best_match)
single_target_scores.append(
best_match_diff)
# Calculate RMS for target angles
target_total = sum([
x**2 for x in single_target_scores
])**0.5 # Tot. score targ/sig
if target_total < best_target_score:
best_target_score = target_total
best_target = target
used_up_targets.append(best_target)
geometry_scores.append(best_target_score)
# Total score is mean of RMS values
geometry_total = np.mean(geometry_scores)
# Record the targets not used for excluding them when deciding for a final geometry
[
not_used.append(target) for target in angles_dict
if target not in used_up_targets
]
all_total.append(
gdata(geometry=geometry,
rms=geometry_total,
coordination=coo,
excluded=not_used,
diff_targets=coo_diff))
# Make a decision here. Starting with the geometry with lowest difference in ideal and observed partners ...
# Check if the difference between the RMS to the next best solution is not larger than 0.5
if not num_targets == 1: # Can't decide for any geoemtry in that case
all_total = sorted(all_total, key=lambda x: abs(x.diff_targets))
for i, total in enumerate(all_total):
next_total = all_total[i + 1]
this_rms, next_rms = total.rms, next_total.rms
diff_to_next = next_rms - this_rms
if diff_to_next > 0.5:
final_geom, final_coo, rms, excluded = total.geometry, total.coordination, total.rms, total.excluded
break
elif next_total.rms < 3.5:
final_geom, final_coo, = next_total.geometry, next_total.coordination
rms, excluded = next_total.rms, next_total.excluded
break
elif i == len(all_total) - 2:
final_geom, final_coo, rms, excluded = "NA", "NA", float(
'nan'), []
break
# Record all contact pairing, excluding those with targets superfluous for chosen geometry
only_water = set([x[0].location for x in contact_pairs]) == {'water'}
if not only_water: # No complex if just with water as targets
logger.info(
f'metal ion {metal.type} complexed with {final_geom} geometry (coo. number {final_coo}/ {num_targets} observed)'
)
for contact_pair in contact_pairs:
target, distance = contact_pair
if target.atom.idx not in excluded:
metal_orig_atom = metal_to_orig_atom[metal]
restype_l, reschain_l, resnr_l = whichrestype(
metal_orig_atom), whichchain(
metal_orig_atom), whichresnumber(metal_orig_atom)
contact = data(metal=metal,
metal_orig_idx=metal_to_id[metal],
metal_type=metal.type,
target=target,
target_orig_idx=target.atom_orig_idx,
target_type=target.type,
coordination_num=final_coo,
distance=distance,
resnr=target.resnr,
restype=target.restype,
reschain=target.reschain,
location=target.location,
rms=rms,
geometry=final_geom,
num_partners=num_targets,
complexnum=cnum + 1,
resnr_l=resnr_l,
restype_l=restype_l,
reschain_l=reschain_l)
pairings.append(contact)
return filter_contacts(pairings)