def sanitize_fragment(mol):
approved_tags = [
"TORSION_ATOMPROP",
"TORSION_ATOMS_FRAGMENT",
"TORSION_ATOMS_ParentMol",
"COUNT",
]
for dp in oechem.OEGetSDDataPairs(mol):
if dp.GetTag() in approved_tags:
continue
oechem.OEDeleteSDData(mol, dp.GetTag())
def delete_tag(mol, tag):
"""
Delete specified SD tag from all conformers of mol.
Parameters
----------
mol: OEChem molecule with all of its conformers
tag: exact string label of the data to delete
"""
for j, conf in enumerate(mol.GetConfs()):
oechem.OEDeleteSDData(conf, tag)
def delete_tag(mol, tag):
"""
Delete specified SD tag from all conformers of mol.
Note: Multi-conformer molecule must be specified
else will get AttributeError:
'OEGraphMol' object has no attribute 'GetConfs'.
Parameters
----------
mol : multi-conformer OEChem molecule
tag : string
exact label of the data to delete
"""
for j, conf in enumerate(mol.GetConfs()):
oechem.OEDeleteSDData(conf, tag)
def FilterMolData(self, mol):
if not oechem.OEHasSDData(mol):
return 0
if self.fields is None:
return -1
if len(self.fields) == 0:
oechem.OEClearSDData(mol)
return 0
validdata = 0
deletefields = []
for dp in oechem.OEGetSDDataPairs(mol):
tag = dp.GetTag()
if tag not in self.fields:
deletefields.append(tag)
continue
value = oechem.OEGetSDData(mol, tag)
if self.asFloating:
try:
float(value)
except ValueError:
oechem.OEThrow.Warning("Failed to convert %s to numeric value (%s) in %s" %
(tag, value, mol.GetTitle()))
deletefields.append(tag)
continue
validdata += 1
if not validdata:
oechem.OEClearSDData(mol)
else:
for nuke in deletefields:
oechem.OEDeleteSDData(mol, nuke)
return validdata
def delete_sd_data(mol, tag, locator_tag):
if oechem.OEHasSDData(mol, locator_tag):
return oechem.OEDeleteSDData(mol, tag)
elif oechem.OEHasSDData(mol.GetActive(), locator_tag):
return oechem.OEDeleteSDData(mol.GetActive(), tag)
return False
f'{molecule.GetTitle()} - {phase}.{ext}')
if not os.path.exists(filename):
files_missing = True
if files_missing:
continue
# Add RUN number
oechem.OESetSDData(molecule, 'run', f'RUN{run_index}')
if args.clean:
for sdpair in oechem.OEGetSDDataPairs(molecule):
if sdpair.GetTag() not in [
'Hybrid2', 'docked_fragment', 'fragments', 'site',
'run'
]:
oechem.OEDeleteSDData(molecule, sdpair.GetTag())
# Copy files
run_dir = os.path.join(args.docked_basedir, 'fah-gromacs',
f'RUN{run_index}')
os.makedirs(run_dir, exist_ok=True)
import shutil
for phase in ['complex', 'ligand']:
for ext in ['gro', 'top']:
src = os.path.join(
gromacs_basedir,
f'{molecule.GetTitle()} - {phase}.{ext}')
dst = os.path.join(run_dir, f'{phase}.{ext}')
shutil.copyfile(src, dst)
oechem.OEWriteMolecule(ofs, molecule)
def DumpSDData(mol):
print("SD data of", mol.GetTitle())
# loop over SD data
for dp in oechem.OEGetSDDataPairs(mol):
print(dp.GetTag(), ':', dp.GetValue())
print()
mol = oechem.OEGraphMol()
oechem.OESmilesToMol(mol, "c1ccccc1")
mol.SetTitle("benzene")
# set some tagged data
oechem.OESetSDData(mol, "color", "brown")
oechem.OESetSDData(mol, oechem.OESDDataPair("size", "small"))
DumpSDData(mol)
# check for existence of data, then delete it
if oechem.OEHasSDData(mol, "size"):
oechem.OEDeleteSDData(mol, "size")
DumpSDData(mol)
# add additional color data
oechem.OEAddSDData(mol, "color", "black")
DumpSDData(mol)
# remove all SD data
oechem.OEClearSDData(mol)
DumpSDData(mol)
# @ </SNIPPET>
def save_profile_as_sd(mol: oechem.OEGraphMol):
oechem.OEDeleteSDData(mol, TOTAL_STRAIN_TAG)
oechem.OESetSDData(mol, TOTAL_STRAIN_TAG, '') # place holder
oechem.OEDeleteSDData(mol, NUM_TORSION_PROFILES_TAG)
oechem.OESetSDData(mol, NUM_TORSION_PROFILES_TAG, '')
oechem.OEDeleteSDData(mol, NUM_LOW_CONFIDENCE_TORSIONS_TAG)
oechem.OESetSDData(mol, NUM_LOW_CONFIDENCE_TORSIONS_TAG, '')
strain_arr = np.zeros(1)
strain_arr_high_conf_preds = np.zeros(1)
num_torsion_profiles = 0
num_low_confidence_torsions = 0
can_torsions = get_canonical_torsions(mol)
for num, can_torsion in enumerate(can_torsions):
bond = mol.GetBond(can_torsion.b, can_torsion.c)
if bond is not None and bond.HasData(ENERGY_PROFILE_TAG):
num_torsion_profiles += 1
bond_strains = bond.GetData(STRAIN_TAG)
profile_offset = bond.GetData(PROFILE_OFFSET_TAG)
if profile_offset < OFFSET_THRESHOLD and (
not bond.HasData(SKIP_TORSION_TAG)):
strain_arr_high_conf_preds += np.array(bond_strains)
strain_arr += np.array(bond_strains)
offset = bond.GetData(PROFILE_OFFSET_TAG)
profile_str = bond.GetData(ENERGY_PROFILE_TAG)
pred_confidence_value = HIGH_PREDICTION_CONFIDENCE_TAG
if offset > OFFSET_THRESHOLD or bond.HasData(SKIP_TORSION_TAG):
profile_str = 'LOW CONFIDENCE - ' + profile_str
pred_confidence_value = LOW_PREDICTION_CONFIDENCE_TAG
num_low_confidence_torsions += 1
#tor_atoms_str = bond.GetData(TORSION_ATOMS_FRAGMENT_TAG)
#tor_atoms_str_list = tor_atoms_str.split(':')
#a_idx, b_idx, c_idx, d_idx = list(map(int, tor_atoms_str_list[0].split()))
tor_atoms_str1 = bond.GetData(TORSION_ATOMS_FRAGMENT_TAG)
ca, cb, cc, cd = list(map(int, tor_atoms_str1.split()))
apStr = "{}:{}:{}:{}".format(ca + 1, cb + 1, cc + 1, cd + 1)
atom_ca = mol.GetAtom(oechem.OEHasAtomIdx(ca))
atom_cb = mol.GetAtom(oechem.OEHasAtomIdx(cb))
atom_cc = mol.GetAtom(oechem.OEHasAtomIdx(cc))
atom_cd = mol.GetAtom(oechem.OEHasAtomIdx(cd))
angle_float = oechem.OEGetTorsion(mol, atom_ca, atom_cb, atom_cc,
atom_cd) * oechem.Rad2Deg
sd_tag1 = 'TORSION_%s_ATOMS' % (num + 1)
sd_tag2 = 'TORSION_%d_TORSIONNET_%s' % (num + 1,
ENERGY_PROFILE_TAG)
sd_tag3 = 'TORSION_%d_TORSIONNET_PRED_CONFIDENCE' % (num + 1)
sd_tag4 = 'TORSION_%d_TORSIONNET_PROFILE_OFFSET' % (num + 1)
oechem.OEDeleteSDData(mol, sd_tag1)
oechem.OEDeleteSDData(mol, sd_tag2)
oechem.OEDeleteSDData(mol, sd_tag3)
oechem.OEDeleteSDData(mol, sd_tag4)
oechem.OESetSDData(mol, sd_tag1, apStr)
oechem.OESetSDData(mol, sd_tag2, profile_str)
sd_tag6 = 'TORSION_%d_%s' % ((num + 1), STRAIN_TAG)
oechem.OEDeleteSDData(mol, sd_tag6)
oechem.OESetSDData(mol, sd_tag6, '%.1f' % bond_strains)
angle = '%.1f' % angle_float
sd_tag5 = 'TORSION_%d_ANGLE' % (num + 1)
oechem.OEDeleteSDData(mol, sd_tag5)
oechem.OESetSDData(mol, sd_tag5, angle)
oechem.OESetSDData(mol, sd_tag3, pred_confidence_value)
oechem.OESetSDData(mol, sd_tag4, '%.2f' % offset)
strain_str = '%.1f' % strain_arr_high_conf_preds[0]
oechem.OESetSDData(mol, TOTAL_STRAIN_TAG, strain_str)
oechem.OESetSDData(mol, NUM_TORSION_PROFILES_TAG,
str(num_torsion_profiles))
oechem.OESetSDData(mol, NUM_LOW_CONFIDENCE_TORSIONS_TAG,
str(num_low_confidence_torsions))
reorder_sd_props(mol)
return mol
if docked_molecule is None:
print('No docking poses available')
import sys
sys.exit(0)
import os
from openeye import oechem, oedocking
# Write molecule as CSV with cleared SD tags
output_filename = os.path.join(docking_basedir, f'{molecule.GetTitle()} - docked.csv')
if not os.path.exists(output_filename):
docked_molecule_clean = docked_molecule.CreateCopy()
for sdpair in oechem.OEGetSDDataPairs(docked_molecule_clean):
if sdpair.GetTag() not in ['Hybrid2', 'fragments', 'site', 'docked_fragment']:
oechem.OEDeleteSDData(docked_molecule_clean, sdpair.GetTag())
with oechem.oemolostream(output_filename) as ofs:
oechem.OEWriteMolecule(ofs, docked_molecule_clean)
# Write molecule as SDF
output_filename = os.path.join(docking_basedir, f'{molecule.GetTitle()} - ligand.sdf')
if not os.path.exists(output_filename):
with oechem.oemolostream(output_filename) as ofs:
oechem.OEWriteMolecule(ofs, docked_molecule)
# Write molecule as mol2
output_filename = os.path.join(docking_basedir, f'{molecule.GetTitle()} - ligand.mol2')
if not os.path.exists(output_filename):
with oechem.oemolostream(output_filename) as ofs:
oechem.OEWriteMolecule(ofs, docked_molecule)
import drconvert
for fragment in tqdm(all_fragments):
filename = f'../docking/{prefix} - docked to {fragment}.oeb'
if os.path.exists(filename):
datarecords = drconvert.RecordConvertToMols(filename)
for molecule in datarecords:
# Annotate which fragment this was docked to
oechem.OESetSDData(molecule, 'fragments', fragment)
if molecule.NumAtoms() > 1000:
# Store protein
molecule.SetTitle(fragment)
receptors[fragment] = oechem.OEMol(molecule)
else:
# Store ligands in best docked poses
oechem.OEDeleteSDData(molecule, 'Number of Confs')
CID = molecule.GetTitle()
if CID not in docked_molecules:
docked_molecules[CID] = oechem.OEMol(molecule)
else:
if score(molecule) < score(docked_molecules[CID]):
docked_molecules[CID] = oechem.OEMol(molecule)
# Sort compounds
docked_molecules = [docked_molecules[CID] for CID in docked_molecules]
docked_molecules.sort(key=score)
# Write all molecules in order of increasing score
print('Writing molecules to CSV...')
filename = f'{prefix} - top docked.csv'
with oechem.oemolostream(filename) as ofs:
def generate_fragalysis(
series: CompoundSeriesAnalysis,
fragalysis_config: FragalysisConfig,
results_path: str,
) -> None:
"""
Generate input and upload to fragalysis from fragalysis_config
Fragalysis spec:https://discuss.postera.ai/t/providing-computed-poses-for-others-to-look-at/1155/8?u=johnchodera
Parameters
----------
series : CompoundSeriesAnalysis
Analysis results
fragalysis_config : FragalysisConfig
Fragalysis input paramters
results_path : str
The path to the results
"""
import os
from openeye import oechem
from rich.progress import track
# make a directory to store fragalysis upload data
fa_path = os.path.join(results_path, "fragalysis_upload")
os.makedirs(fa_path, exist_ok=True)
ref_mols = fragalysis_config.ref_mols # e.g. x12073
ref_pdb = fragalysis_config.ref_pdb # e.g. x12073
# set paths
ligands_path = os.path.join(results_path,
fragalysis_config.ligands_filename)
fa_ligands_path = os.path.join(fa_path,
fragalysis_config.fragalysis_sdf_filename)
# copy sprint generated sdf to new name for fragalysis input
from shutil import copyfile
copyfile(ligands_path, fa_ligands_path)
# Read ligand poses
molecules = []
with oechem.oemolistream(ligands_path) as ifs:
oemol = oechem.OEGraphMol()
while oechem.OEReadMolecule(ifs, oemol):
molecules.append(oemol.CreateCopy())
print(f"{len(molecules)} ligands read")
# Get zipped PDB if specified
if fragalysis_config.ref_pdb == "references.zip":
consolidate_protein_snapshots_into_pdb(
oemols=molecules,
results_path=results_path,
pdb_filename="references.pdb",
fragalysis_input=True,
fragalysis_path=fa_path,
)
descriptions = {
"DDG (kcal/mol)":
"Relative computed free energy difference",
"dDDG (kcal/mol)":
"Uncertainty in computed relative free energy difference",
"ref_mols":
"a comma separated list of the fragments that inspired the design of the new molecule (codes as they appear in fragalysis - e.g. x0104_0,x0692_0)",
"ref_pdb":
"The name of the fragment (and corresponding Mpro fragment structure) with the best scoring hybrid docking pose",
"original SMILES":
"the original SMILES of the compound before any computation was carried out",
}
# Preprocess molecules
tags_to_retain = {"DDG (kcal/mol)", "dDDG (kcal/mol)"}
index = 0
for oemol in track(molecules, "Preprocessing molecules for Fragalysis..."):
# Remove hydogrens
oechem.OESuppressHydrogens(oemol, True)
# Get original SMILES
original_smiles = oechem.OEGetSDData(oemol, "SMILES")
# Remove irrelevant SD tags
for sdpair in oechem.OEGetSDDataPairs(oemol):
tag = sdpair.GetTag()
value = sdpair.GetValue()
if tag not in tags_to_retain:
oechem.OEDeleteSDData(oemol, tag)
# Add required SD tags
oechem.OESetSDData(oemol, "ref_mols", fragalysis_config.ref_mols)
# If ref_pdb is zip file, use this
if fragalysis_config.ref_pdb == "references.zip":
oechem.OESetSDData(oemol, "ref_pdb",
f"references/references_{index}.pdb"),
index += 1
else:
oechem.OESetSDData(oemol, "ref_pdb", fragalysis_config.ref_pdb)
oechem.OESetSDData(oemol, "original SMILES", original_smiles)
# Add initial blank molecule (that includes distances)
import copy
from datetime import datetime
# Find a molecule that includes distances, if present
oemol = molecules[0].CreateCopy()
# Add descriptions to each SD field
for sdpair in oechem.OEGetSDDataPairs(oemol):
tag = sdpair.GetTag()
value = sdpair.GetValue()
oechem.OESetSDData(oemol, tag, descriptions[tag])
# Add other fields
oemol.SetTitle("ver_1.2")
oechem.OESetSDData(oemol, "ref_url", fragalysis_config.ref_url)
oechem.OESetSDData(oemol, "submitter_name",
fragalysis_config.submitter_name)
oechem.OESetSDData(oemol, "submitter_email",
fragalysis_config.submitter_email)
oechem.OESetSDData(oemol, "submitter_institution",
fragalysis_config.submitter_institution)
oechem.OESetSDData(oemol, "generation_date",
datetime.today().strftime("%Y-%m-%d"))
oechem.OESetSDData(oemol, "method", fragalysis_config.method)
molecules.insert(0, oemol) # make it first molecule
# Write sorted molecules
with oechem.oemolostream(fa_ligands_path) as ofs:
for oemol in track(molecules,
description="Writing Fragalysis SDF file..."):
oechem.OEWriteMolecule(ofs, oemol)
# TODO add check SDF step here?
# Upload to fragalysis
print("Uploading to Fragalysis...")
print(f"--> Target: {fragalysis_config.target_name}")
from fragalysis_api.xcextracter.computed_set_update import update_cset, REQ_URL
if fragalysis_config.new_upload:
update_set = "None" # new upload
print(f"--> Uploading a new set")
else:
update_set = ("".join(fragalysis_config.submitter_name.split()) + "-" +
"".join(fragalysis_config.method.split()))
print(f"--> Updating set: {update_set}")
if fragalysis_config.ref_pdb == "references.zip":
pdb_zip_path = os.path.join(fa_path, "references.zip")
else:
pdb_zip_path = None
taskurl = update_cset(
REQ_URL,
target_name=fragalysis_config.target_name,
sdf_path=fa_ligands_path,
pdb_zip_path=pdb_zip_path,
update_set=update_set,
upload_key=fragalysis_config.upload_key,
submit_choice=1,
add=False,
)
print(f"Upload complete, check upload status: {taskurl}")
def RemoveProps(proplist, ifs, ofs):
for mol in ifs.GetOEGraphMols():
for tag in proplist:
oechem.OEDeleteSDData(mol, tag)
oechem.OEWriteMolecule(ofs, mol)
def KeepProps(proplist, ifs, ofs):
for mol in ifs.GetOEGraphMols():
for dp in oechem.OEGetSDDataPairs(mol):
if dp.GetTag() not in proplist:
oechem.OEDeleteSDData(mol, dp.GetTag())
oechem.OEWriteMolecule(ofs, mol)