File size: 14,839 Bytes
6d19a18 | 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 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217 218 219 220 221 222 223 224 225 226 227 228 229 230 231 232 233 234 235 236 237 238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 257 258 259 260 261 262 263 264 265 266 267 268 269 270 271 272 273 274 275 276 277 278 279 280 281 282 283 284 285 286 287 288 289 290 291 292 293 294 295 296 297 298 299 300 301 302 303 304 305 306 307 308 309 310 311 312 313 314 315 316 317 318 319 320 321 322 323 324 325 326 327 328 329 330 331 332 333 334 335 336 337 338 339 340 341 342 343 344 345 346 347 348 349 350 351 352 353 354 355 356 357 358 359 360 361 362 363 364 365 366 367 368 369 370 371 372 373 374 375 376 377 378 379 380 381 382 383 384 385 386 387 388 389 390 391 392 393 394 395 396 397 398 399 400 401 402 403 404 405 406 407 408 409 410 411 412 413 414 415 416 417 418 419 420 421 422 423 424 425 426 427 428 429 | #!/usr/bin/env python3
"""Run one docking method over a prepared OpenBind docking-mode directory."""
from __future__ import annotations
import argparse
import shlex
import shutil
import subprocess
import sys
import time
from pathlib import Path
from rdkit import Chem
from rdkit.Chem import rdMolTransforms
from datetime import datetime
Coord3D = tuple[float, float, float]
SUPPORTED_ENGINES = {"gnina", "smina", "diffdock"}
def log(message: str) -> None:
"""Print a timestamped status message."""
timestamp = datetime.now().strftime("%Y-%m-%d %H:%M:%S")
print(f"[{timestamp}] {message}", flush=True)
def validate_file(path: Path, label: str) -> Path:
"""Require a non-empty input file."""
if not path.is_file():
raise FileNotFoundError(f"Missing {label}: {path}")
if path.stat().st_size == 0:
raise ValueError(f"Empty {label}: {path}")
return path
def compute_centroid(sdf_path: Path) -> Coord3D:
"""Return the centroid of the first conformer in an SDF file."""
mol = Chem.MolFromMolFile(str(sdf_path), removeHs=False)
if mol is None or mol.GetNumConformers() == 0:
raise ValueError(f"RDKit could not read a 3D ligand from: {sdf_path}")
centroid = rdMolTransforms.ComputeCentroid(mol.GetConformer(0))
return float(centroid.x), float(centroid.y), float(centroid.z)
def reference_complex_dir(mode_dir: Path, complex_id: str) -> Path:
"""Return the redock directory providing ligand inputs and reference poses."""
root = mode_dir if mode_dir.name == "redock" else mode_dir.parent / "redock"
complex_dir = root / complex_id
if not complex_dir.is_dir():
raise FileNotFoundError(f"Redock complex directory not found: {complex_dir}")
return complex_dir
def receptor_path(
complex_dir: Path,
complex_id: str,
mode_label: str,
) -> Path:
"""Resolve the receptor file using the fixed prepared-input naming scheme."""
if mode_label == "redock":
return validate_file(complex_dir / f"{complex_id}_prepared.pdb", "receptor")
if mode_label == "fragment_crossdock":
matches = sorted(complex_dir.glob("fragment_crossdock_*_aligned.pdb"))
if len(matches) != 1:
raise FileNotFoundError(
f"Expected exactly one fragment-crossdock receptor in {complex_dir}; "
f"found {len(matches)}"
)
return validate_file(matches[0], "receptor")
return validate_file(
complex_dir / f"{mode_label}_prepared_aligned.pdb",
"receptor",
)
def ligand_input_path(reference_dir: Path, complex_id: str, input_num: int) -> Path:
"""Return one prepared ligand conformer."""
return validate_file(
reference_dir / f"{complex_id}_ligand_prepared_{input_num}.sdf",
"ligand input",
)
def reference_ligand_path(reference_dir: Path, complex_id: str) -> Path:
"""Return the crystallographic ligand used for docking-box placement."""
return validate_file(
reference_dir / f"{complex_id}_reference_ligand.sdf",
"reference ligand",
)
def build_box_args(
size: str,
reference_ligand: Path,
centre: Coord3D | None,
) -> list[str]:
"""Build GNINA/Smina box arguments."""
if size.startswith("autobox"):
parts = size.split("_", maxsplit=1)
args = ["--autobox_ligand", str(reference_ligand)]
if len(parts) == 2:
try:
float(parts[1])
except ValueError as exc:
raise ValueError(f"Invalid autobox size: {size}") from exc
args += ["--autobox_add", parts[1]]
return args
try:
box_size = float(size)
except ValueError as exc:
raise ValueError(
"--size must be numeric or use the form autobox[_ADD]"
) from exc
if box_size <= 0:
raise ValueError("--size must be greater than zero")
x, y, z = centre if centre is not None else compute_centroid(reference_ligand)
return [
"--center_x",
str(x),
"--center_y",
str(y),
"--center_z",
str(z),
"--size_x",
str(box_size),
"--size_y",
str(box_size),
"--size_z",
str(box_size),
]
def add_cnn_model_args(command: list[str], cnn_model: str | None) -> None:
"""Append GNINA CNN model arguments."""
if cnn_model in (None, "default"):
return
path = Path(cnn_model).expanduser().resolve()
if path.is_file():
command += ["--cnn_model", str(path)]
return
if path.is_dir():
models = sorted(path.glob("*.pt"))
if not models:
raise FileNotFoundError(f"No .pt models found in: {path}")
command.extend(["--cnn_model", *map(str, models)])
return
raise FileNotFoundError(f"CNN model path not found: {path}")
def diffdock_complete(poses_dir: Path, num_modes: int) -> bool:
"""Return whether a DiffDock run already contains the requested pose count."""
poses = sorted(poses_dir.glob("rank*_confidence*.sdf"))
return len(poses) >= num_modes and all(path.stat().st_size > 0 for path in poses)
def run_docking(
complex_dir: Path,
mode_dir: Path,
complex_id: str,
engine: str,
method: Path,
method_label: str,
mode_label: str,
output_dir: Path,
input_num: int,
num_modes: int,
exhaustiveness: int,
size: str,
seed: int,
scoring: str | None,
cnn_model: str | None,
centre: Coord3D | None,
overwrite: bool,
) -> tuple[int, Path, Path]:
"""Run one docking task and return the exit code and output paths."""
receptor = receptor_path(complex_dir, complex_id, mode_label)
reference_dir = reference_complex_dir(mode_dir, complex_id)
ligand_input = ligand_input_path(reference_dir, complex_id, input_num)
reference_ligand = reference_ligand_path(reference_dir, complex_id)
setup_label = f"{method_label}_{mode_label}"
seed_dir = output_dir / setup_label / complex_id / f"seed_{seed}"
poses_dir = seed_dir / "docked_poses"
poses_dir.mkdir(parents=True, exist_ok=True)
log_file = seed_dir / f"{complex_id}_{input_num}.log"
if engine == "diffdock":
if not overwrite and diffdock_complete(poses_dir, num_modes):
return 0, poses_dir, log_file
command = [
sys.executable,
"inference.py",
"--config",
"default_inference_args.yaml",
"--protein_path",
str(receptor),
"--ligand_description",
str(ligand_input),
"--out_dir",
str(seed_dir),
"--complex_name",
poses_dir.name,
]
cwd = method
expected_output: Path | None = None
else:
expected_output = poses_dir / f"{complex_id}_docked_{input_num}.sdf"
if (
not overwrite
and expected_output.is_file()
and expected_output.stat().st_size > 0
):
return 0, poses_dir, log_file
command = [
str(method),
"--receptor",
str(receptor),
"--ligand",
str(ligand_input),
"--out",
str(expected_output),
"--exhaustiveness",
str(exhaustiveness),
"--num_modes",
str(num_modes),
"--seed",
str(seed),
*build_box_args(size, reference_ligand, centre),
]
if scoring is not None:
command += ["--scoring", scoring]
if engine == "gnina":
add_cnn_model_args(command, cnn_model)
cwd = None
with log_file.open("w", encoding="utf-8") as handle:
handle.write(shlex.join(command) + "\n\n")
handle.flush()
result = subprocess.run(
command,
stdout=handle,
stderr=subprocess.STDOUT,
cwd=cwd,
check=False,
)
if result.returncode == 0 and expected_output is not None:
validate_file(expected_output, "docking output")
return result.returncode, poses_dir, log_file
def parse_centre(args: argparse.Namespace) -> Coord3D | None:
"""Parse an optional explicit docking-box centre."""
values = (args.x_coord, args.y_coord, args.z_coord)
if any(value is not None for value in values) and not all(
value is not None for value in values
):
raise ValueError("Provide all of --x-coord, --y-coord and --z-coord, or none")
if values[0] is None:
return None
return float(values[0]), float(values[1]), float(values[2])
def find_complexes(mode_dir: Path, complex_id: str | None) -> list[Path]:
"""Return selected prepared complex directories."""
if complex_id is not None:
path = mode_dir / complex_id
if not path.is_dir():
raise FileNotFoundError(f"Complex directory not found: {path}")
return [path]
complexes = sorted(path for path in mode_dir.iterdir() if path.is_dir())
if not complexes:
raise ValueError(f"No complex directories found in {mode_dir}")
return complexes
def validate_method(engine: str, method: Path) -> Path:
"""Validate the configured docking executable or DiffDock directory."""
path = method.expanduser().resolve()
if engine == "diffdock":
if not path.is_dir() or not (path / "inference.py").is_file():
raise FileNotFoundError(
f"DiffDock directory or inference.py not found: {path}"
)
elif not path.is_file():
raise FileNotFoundError(f"Docking executable not found: {path}")
return path
def build_parser() -> argparse.ArgumentParser:
"""Build the command-line parser."""
parser = argparse.ArgumentParser(description=__doc__)
parser.add_argument(
"mode_dir", type=Path, help="Prepared directory for one docking mode."
)
parser.add_argument("--engine", required=True, choices=sorted(SUPPORTED_ENGINES))
parser.add_argument(
"--method",
required=True,
type=Path,
help="Executable or DiffDock directory.",
)
parser.add_argument(
"--method-label", required=True, help="Method label used in output paths."
)
parser.add_argument(
"--mode-label", required=True, help="Prepared mode directory name."
)
parser.add_argument(
"--output-dir", required=True, type=Path, help="Docking output root."
)
parser.add_argument("--exhaustiveness", type=int, default=8)
parser.add_argument("--num-inputs", type=int, default=1)
parser.add_argument("--num-modes", type=int, default=8)
parser.add_argument("--size", default="25", help="Box size or autobox[_ADD].")
parser.add_argument("--seed", type=int, default=1)
parser.add_argument("--scoring", default=None)
parser.add_argument("--cnn-model", default=None)
parser.add_argument("--complex-id", default=None, help="Run one complex only.")
parser.add_argument("--overwrite", action="store_true")
parser.add_argument("--x-coord", type=float, default=None)
parser.add_argument("--y-coord", type=float, default=None)
parser.add_argument("--z-coord", type=float, default=None)
return parser
def main() -> None:
"""Run docking across the selected complexes."""
args = build_parser().parse_args()
mode_dir = args.mode_dir.expanduser().resolve()
if not mode_dir.is_dir():
raise FileNotFoundError(f"Prepared mode directory not found: {mode_dir}")
if args.mode_label != mode_dir.name:
raise ValueError(
f"--mode-label must match the prepared directory name exactly: {mode_dir.name}"
)
if args.num_inputs < 1 or args.num_modes < 1 or args.exhaustiveness < 1:
raise ValueError(
"--num-inputs, --num-modes and --exhaustiveness must be positive"
)
method = validate_method(args.engine, args.method)
output_dir = args.output_dir.expanduser().resolve()
centre = parse_centre(args)
complexes = find_complexes(mode_dir, args.complex_id)
num_inputs = 1 if args.engine == "diffdock" else args.num_inputs
log(f"Prepared mode: {mode_dir}")
log(f"Output root: {output_dir}")
log(f"Method: {args.method_label} ({args.engine})")
log(f"Complexes: {len(complexes)}")
start = time.time()
failures: list[tuple[str, str, Path | None]] = []
succeeded = 0
attempted = 0
for complex_dir in complexes:
complex_id = complex_dir.name
if args.overwrite:
seed_dir = (
output_dir
/ f"{args.method_label}_{args.mode_label}"
/ complex_id
/ f"seed_{args.seed}"
)
if seed_dir.exists():
shutil.rmtree(seed_dir)
for input_num in range(1, num_inputs + 1):
attempted += 1
task_id = f"{complex_id}_{input_num}"
log(f"-> {task_id} ...")
try:
return_code, poses_dir, log_file = run_docking(
complex_dir=complex_dir,
mode_dir=mode_dir,
complex_id=complex_id,
engine=args.engine,
method=method,
method_label=args.method_label,
mode_label=args.mode_label,
output_dir=output_dir,
input_num=input_num,
num_modes=args.num_modes,
exhaustiveness=args.exhaustiveness,
size=str(args.size),
seed=args.seed,
scoring=args.scoring,
cnn_model=args.cnn_model,
centre=centre,
overwrite=args.overwrite,
)
except Exception as exc:
log(f" ERROR: {exc}")
failures.append((task_id, str(exc), None))
continue
if return_code == 0:
succeeded += 1
log(" OK")
else:
log(f" FAILED (exit {return_code})")
failures.append((task_id, f"exit code {return_code}", log_file))
elapsed = time.strftime("%H:%M:%S", time.gmtime(time.time() - start))
success_pct = 100.0 * succeeded / attempted if attempted else 0.0
log(
f"Summary: complexes={len(complexes)}, tasks={attempted}, "
f"succeeded={succeeded} ({success_pct:.1f}%), failed={len(failures)}"
)
log(f"Elapsed time: {elapsed}")
if failures:
for task_id, error, log_file in failures:
log_text = f"; log={log_file}" if log_file is not None else ""
log(f" - {task_id}: {error}{log_text}")
raise SystemExit(1)
if __name__ == "__main__":
main()
|