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714cf46 | 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217 218 219 220 221 222 223 224 225 226 227 228 229 230 231 232 233 234 235 236 237 238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 257 258 259 260 261 262 263 264 265 266 267 268 269 270 271 272 273 274 275 276 277 278 279 280 281 282 283 284 285 286 287 288 289 290 291 292 293 294 295 296 | """Compute conformers and symmetries for all the CCD molecules."""
import argparse
import multiprocessing
import pickle
import sys
from functools import partial
from pathlib import Path
import pandas as pd
import rdkit
from p_tqdm import p_uimap
from pdbeccdutils.core import ccd_reader
from pdbeccdutils.core.component import ConformerType
from rdkit import rdBase
from rdkit.Chem import AllChem
from rdkit.Chem.rdchem import Conformer, Mol
from tqdm import tqdm
def load_molecules(components: str) -> list[Mol]:
"""Load the CCD components file.
Parameters
----------
components : str
Path to the CCD components file.
Returns
-------
list[Mol]
"""
components: dict[str, ccd_reader.CCDReaderResult]
components = ccd_reader.read_pdb_components_file(components)
mols = []
for name, component in components.items():
mol = component.component.mol
mol.SetProp("PDB_NAME", name)
mols.append(mol)
return mols
def compute_3d(mol: Mol, version: str = "v3") -> bool:
"""Generate 3D coordinates using EKTDG method.
Taken from `pdbeccdutils.core.component.Component`.
Parameters
----------
mol: Mol
The RDKit molecule to process
version: str, optional
The ETKDG version, defaults ot v3
Returns
-------
bool
Whether computation was successful.
"""
if version == "v3":
options = rdkit.Chem.AllChem.ETKDGv3()
elif version == "v2":
options = rdkit.Chem.AllChem.ETKDGv2()
else:
options = rdkit.Chem.AllChem.ETKDGv2()
options.clearConfs = False
conf_id = -1
try:
conf_id = rdkit.Chem.AllChem.EmbedMolecule(mol, options)
rdkit.Chem.AllChem.UFFOptimizeMolecule(mol, confId=conf_id, maxIters=1000)
except RuntimeError:
pass # Force field issue here
except ValueError:
pass # sanitization issue here
if conf_id != -1:
conformer = mol.GetConformer(conf_id)
conformer.SetProp("name", ConformerType.Computed.name)
conformer.SetProp("coord_generation", f"ETKDG{version}")
return True
return False
def get_conformer(mol: Mol, c_type: ConformerType) -> Conformer:
"""Retrieve an rdkit object for a deemed conformer.
Taken from `pdbeccdutils.core.component.Component`.
Parameters
----------
mol: Mol
The molecule to process.
c_type: ConformerType
The conformer type to extract.
Returns
-------
Conformer
The desired conformer, if any.
Raises
------
ValueError
If there are no conformers of the given tyoe.
"""
for c in mol.GetConformers():
try:
if c.GetProp("name") == c_type.name:
return c
except KeyError: # noqa: PERF203
pass
msg = f"Conformer {c_type.name} does not exist."
raise ValueError(msg)
def compute_symmetries(mol: Mol) -> list[list[int]]:
"""Compute the symmetries of a molecule.
Parameters
----------
mol : Mol
The molecule to process
Returns
-------
list[list[int]]
The symmetries as a list of index permutations
"""
mol = AllChem.RemoveHs(mol)
idx_map = {}
atom_idx = 0
for i, atom in enumerate(mol.GetAtoms()):
# Skip if leaving atoms
if int(atom.GetProp("leaving_atom")):
continue
idx_map[i] = atom_idx
atom_idx += 1
# Calculate self permutations
permutations = []
raw_permutations = mol.GetSubstructMatches(mol, uniquify=False)
for raw_permutation in raw_permutations:
# Filter out permutations with leaving atoms
try:
if {raw_permutation[idx] for idx in idx_map} == set(idx_map.keys()):
permutation = [
idx_map[idx] for idx in raw_permutation if idx in idx_map
]
permutations.append(permutation)
except Exception: # noqa: S110, PERF203, BLE001
pass
serialized_permutations = pickle.dumps(permutations)
mol.SetProp("symmetries", serialized_permutations.hex())
return permutations
def process(mol: Mol, output: str) -> tuple[str, str]:
"""Process a CCD component.
Parameters
----------
mol : Mol
The molecule to process
output : str
The directory to save the molecules
Returns
-------
str
The name of the component
str
The result of the conformer generation
"""
# Get name
name = mol.GetProp("PDB_NAME")
# Check if single atom
if mol.GetNumAtoms() == 1:
result = "single"
else:
# Get the 3D conformer
try:
# Try to generate a 3D conformer with RDKit
success = compute_3d(mol, version="v3")
if success:
_ = get_conformer(mol, ConformerType.Computed)
result = "computed"
# Otherwise, default to the ideal coordinates
else:
_ = get_conformer(mol, ConformerType.Ideal)
result = "ideal"
except ValueError:
result = "failed"
# Dump the molecule
path = Path(output) / f"{name}.pkl"
with path.open("wb") as f:
pickle.dump(mol, f)
# Output the results
return name, result
def main(args: argparse.Namespace) -> None:
"""Process conformers."""
# Set property saving
rdkit.Chem.SetDefaultPickleProperties(rdkit.Chem.PropertyPickleOptions.AllProps)
# Load components
print("Loading components") # noqa: T201
molecules = load_molecules(args.components)
# Reset stdout and stderr, as pdbccdutils messes with them
sys.stdout = sys.__stdout__
sys.stderr = sys.__stderr__
# Disable rdkit warnings
blocker = rdBase.BlockLogs() # noqa: F841
# Setup processing function
outdir = Path(args.outdir)
outdir.mkdir(parents=True, exist_ok=True)
mol_output = outdir / "mols"
mol_output.mkdir(parents=True, exist_ok=True)
process_fn = partial(process, output=str(mol_output))
# Process the files in parallel
print("Processing components") # noqa: T201
metadata = []
# Check if we can run in parallel
max_processes = multiprocessing.cpu_count()
num_processes = max(1, min(args.num_processes, max_processes, len(molecules)))
parallel = num_processes > 1
if parallel:
for name, result in p_uimap(
process_fn,
molecules,
num_cpus=num_processes,
):
metadata.append({"name": name, "result": result})
else:
for mol in tqdm(molecules):
name, result = process_fn(mol)
metadata.append({"name": name, "result": result})
# Load and group outputs
molecules = {}
for item in metadata:
if item["result"] == "failed":
continue
# Load the mol file
path = mol_output / f"{item['name']}.pkl"
with path.open("rb") as f:
mol = pickle.load(f) # noqa: S301
molecules[item["name"]] = mol
# Dump metadata
path = outdir / "results.csv"
metadata = pd.DataFrame(metadata)
metadata.to_csv(path)
# Dump the components
path = outdir / "ccd.pkl"
with path.open("wb") as f:
pickle.dump(molecules, f)
if __name__ == "__main__":
parser = argparse.ArgumentParser()
parser.add_argument("--components", type=str)
parser.add_argument("--outdir", type=str)
parser.add_argument(
"--num_processes",
type=int,
default=multiprocessing.cpu_count(),
)
args = parser.parse_args()
main(args)
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