boltz-vsynthes 0.0.12__py3-none-any.whl → 0.0.14__py3-none-any.whl

boltz/utils/sdf_to_pre_affinity_npz.py

@@ -1,35 +1,1286 @@
-#!/usr/bin/env python3
-"""
-boltz-sdf-to-pre-affinity: Convert a docked SDF file (protein-ligand complex) to Boltz pre_affinity_[ligand_id].npz format.
+import multiprocessing
+import os
+import pickle
+import platform
+import tarfile
+import urllib.request
+import warnings
+from dataclasses import asdict, dataclass
+from functools import partial
+from multiprocessing import Pool
+from pathlib import Path
+from typing import Literal, Optional
 
-Usage:
-    boltz-sdf-to-pre-affinity --sdf docked_pose.sdf --ligand_id ligand1 --output pre_affinity_ligand1.npz
+import click
+import torch
+from pytorch_lightning import Trainer, seed_everything
+from pytorch_lightning.strategies import DDPStrategy
+from pytorch_lightning.utilities import rank_zero_only
+from rdkit import Chem
+from tqdm import tqdm
 
-This command is available after installing boltz with pip.
-"""
-import argparse
-from pathlib import Path
+from boltz.data import const
+from boltz.data.module.inference import BoltzInferenceDataModule
+from boltz.data.module.inferencev2 import Boltz2InferenceDataModule
+from boltz.data.mol import load_canonicals
+from boltz.data.msa.mmseqs2 import run_mmseqs2
+from boltz.data.parse.a3m import parse_a3m
+from boltz.data.parse.csv import parse_csv
+from boltz.data.parse.fasta import parse_fasta
+from boltz.data.parse.yaml import parse_yaml
+from boltz.data.types import MSA, Manifest, Record
+from boltz.data.write.writer import BoltzAffinityWriter, BoltzWriter
+from boltz.model.models.boltz1 import Boltz1
+from boltz.model.models.boltz2 import Boltz2
+
+CCD_URL = "https://huggingface.co/boltz-community/boltz-1/resolve/main/ccd.pkl"
+MOL_URL = "https://huggingface.co/boltz-community/boltz-2/resolve/main/mols.tar"
+
+BOLTZ1_URL_WITH_FALLBACK = [
+    "https://model-gateway.boltz.bio/boltz1_conf.ckpt",
+    "https://huggingface.co/boltz-community/boltz-1/resolve/main/boltz1_conf.ckpt",
+]
+
+BOLTZ2_URL_WITH_FALLBACK = [
+    "https://model-gateway.boltz.bio/boltz2_conf.ckpt",
+    "https://huggingface.co/boltz-community/boltz-2/resolve/main/boltz2_conf.ckpt",
+]
+
+BOLTZ2_AFFINITY_URL_WITH_FALLBACK = [
+    "https://model-gateway.boltz.bio/boltz2_aff.ckpt",
+    "https://huggingface.co/boltz-community/boltz-2/resolve/main/boltz2_aff.ckpt",
+]
+
+
+@dataclass
+class BoltzProcessedInput:
+    """Processed input data."""
+
+    manifest: Manifest
+    targets_dir: Path
+    msa_dir: Path
+    constraints_dir: Optional[Path] = None
+    template_dir: Optional[Path] = None
+    extra_mols_dir: Optional[Path] = None
+
+
+@dataclass
+class PairformerArgs:
+    """Pairformer arguments."""
+
+    num_blocks: int = 48
+    num_heads: int = 16
+    dropout: float = 0.0
+    activation_checkpointing: bool = False
+    offload_to_cpu: bool = False
+    v2: bool = False
+
+
+@dataclass
+class PairformerArgsV2:
+    """Pairformer arguments."""
+
+    num_blocks: int = 64
+    num_heads: int = 16
+    dropout: float = 0.0
+    activation_checkpointing: bool = False
+    offload_to_cpu: bool = False
+    v2: bool = True
+
+
+@dataclass
+class MSAModuleArgs:
+    """MSA module arguments."""
+
+    msa_s: int = 64
+    msa_blocks: int = 4
+    msa_dropout: float = 0.0
+    z_dropout: float = 0.0
+    use_paired_feature: bool = True
+    pairwise_head_width: int = 32
+    pairwise_num_heads: int = 4
+    activation_checkpointing: bool = False
+    offload_to_cpu: bool = False
+    subsample_msa: bool = False
+    num_subsampled_msa: int = 1024
+
+
+@dataclass
+class BoltzDiffusionParams:
+    """Diffusion process parameters."""
+
+    gamma_0: float = 0.605
+    gamma_min: float = 1.107
+    noise_scale: float = 0.901
+    rho: float = 8
+    step_scale: float = 1.638
+    sigma_min: float = 0.0004
+    sigma_max: float = 160.0
+    sigma_data: float = 16.0
+    P_mean: float = -1.2
+    P_std: float = 1.5
+    coordinate_augmentation: bool = True
+    alignment_reverse_diff: bool = True
+    synchronize_sigmas: bool = True
+    use_inference_model_cache: bool = True
+
+
+@dataclass
+class Boltz2DiffusionParams:
+    """Diffusion process parameters."""
+
+    gamma_0: float = 0.8
+    gamma_min: float = 1.0
+    noise_scale: float = 1.003
+    rho: float = 7
+    step_scale: float = 1.5
+    sigma_min: float = 0.0001
+    sigma_max: float = 160.0
+    sigma_data: float = 16.0
+    P_mean: float = -1.2
+    P_std: float = 1.5
+    coordinate_augmentation: bool = True
+    alignment_reverse_diff: bool = True
+    synchronize_sigmas: bool = True
+
+
+@dataclass
+class BoltzSteeringParams:
+    """Steering parameters."""
+
+    fk_steering: bool = True
+    num_particles: int = 3
+    fk_lambda: float = 4.0
+    fk_resampling_interval: int = 3
+    guidance_update: bool = True
+    num_gd_steps: int = 20
+
+
+@rank_zero_only
+def download_boltz1(cache: Path) -> None:
+    """Download all the required data.
+
+    Parameters
+    ----------
+    cache : Path
+        The cache directory.
+
+    """
+    # Download CCD
+    ccd = cache / "ccd.pkl"
+    if not ccd.exists():
+        click.echo(
+            f"Downloading the CCD dictionary to {ccd}. You may "
+            "change the cache directory with the --cache flag."
+        )
+        urllib.request.urlretrieve(CCD_URL, str(ccd))  # noqa: S310
+
+    # Download model
+    model = cache / "boltz1_conf.ckpt"
+    if not model.exists():
+        click.echo(
+            f"Downloading the model weights to {model}. You may "
+            "change the cache directory with the --cache flag."
+        )
+        for i, url in enumerate(BOLTZ1_URL_WITH_FALLBACK):
+            try:
+                urllib.request.urlretrieve(url, str(model))  # noqa: S310
+                break
+            except Exception as e:  # noqa: BLE001
+                if i == len(BOLTZ1_URL_WITH_FALLBACK) - 1:
+                    msg = f"Failed to download model from all URLs. Last error: {e}"
+                    raise RuntimeError(msg) from e
+                continue
+
+
+@rank_zero_only
+def download_boltz2(cache: Path) -> None:
+    """Download all the required data.
+
+    Parameters
+    ----------
+    cache : Path
+        The cache directory.
+
+    """
+    # Download CCD
+    mols = cache / "mols"
+    tar_mols = cache / "mols.tar"
+    if not tar_mols.exists():
+        click.echo(
+            f"Downloading the CCD data to {tar_mols}. "
+            "This may take a bit of time. You may change the cache directory "
+            "with the --cache flag."
+        )
+        urllib.request.urlretrieve(MOL_URL, str(tar_mols))  # noqa: S310
+    if not mols.exists():
+        click.echo(
+            f"Extracting the CCD data to {mols}. "
+            "This may take a bit of time. You may change the cache directory "
+            "with the --cache flag."
+        )
+        with tarfile.open(str(tar_mols), "r") as tar:
+            tar.extractall(cache)  # noqa: S202
+
+    # Download model
+    model = cache / "boltz2_conf.ckpt"
+    if not model.exists():
+        click.echo(
+            f"Downloading the Boltz-2 weights to {model}. You may "
+            "change the cache directory with the --cache flag."
+        )
+        for i, url in enumerate(BOLTZ2_URL_WITH_FALLBACK):
+            try:
+                urllib.request.urlretrieve(url, str(model))  # noqa: S310
+                break
+            except Exception as e:  # noqa: BLE001
+                if i == len(BOLTZ2_URL_WITH_FALLBACK) - 1:
+                    msg = f"Failed to download model from all URLs. Last error: {e}"
+                    raise RuntimeError(msg) from e
+                continue
+
+    # Download affinity model
+    affinity_model = cache / "boltz2_aff.ckpt"
+    if not affinity_model.exists():
+        click.echo(
+            f"Downloading the Boltz-2 affinity weights to {affinity_model}. You may "
+            "change the cache directory with the --cache flag."
+        )
+        for i, url in enumerate(BOLTZ2_AFFINITY_URL_WITH_FALLBACK):
+            try:
+                urllib.request.urlretrieve(url, str(affinity_model))  # noqa: S310
+                break
+            except Exception as e:  # noqa: BLE001
+                if i == len(BOLTZ2_AFFINITY_URL_WITH_FALLBACK) - 1:
+                    msg = f"Failed to download model from all URLs. Last error: {e}"
+                    raise RuntimeError(msg) from e
+                continue
+
+
+def get_cache_path() -> str:
+    """Determine the cache path, prioritising the BOLTZ_CACHE environment variable.
+
+    Returns
+    -------
+    str: Path
+        Path to use for boltz cache location.
+
+    """
+    env_cache = os.environ.get("BOLTZ_CACHE")
+    if env_cache:
+        resolved_cache = Path(env_cache).expanduser().resolve()
+        if not resolved_cache.is_absolute():
+            msg = f"BOLTZ_CACHE must be an absolute path, got: {env_cache}"
+            raise ValueError(msg)
+        return str(resolved_cache)
+
+    return str(Path("~/.boltz").expanduser())
+
+
+def check_inputs(data: Path) -> list[Path]:
+    """Check the input data and output directory.
+
+    Parameters
+    ----------
+    data : Path
+        The input data.
+
+    Returns
+    -------
+    list[Path]
+        The list of input data.
+
+    """
+    click.echo("Checking input data.")
+
+    # Check if data is a directory
+    if data.is_dir():
+        data: list[Path] = list(data.glob("*"))
+
+        # Filter out non .fasta or .yaml files, raise
+        # an error on directory and other file types
+        for d in data:
+            if d.is_dir():
+                msg = f"Found directory {d} instead of .fasta or .yaml."
+                raise RuntimeError(msg)
+            if d.suffix not in (".fa", ".fas", ".fasta", ".yml", ".yaml"):
+                msg = (
+                    f"Unable to parse filetype {d.suffix}, "
+                    "please provide a .fasta or .yaml file."
+                )
+                raise RuntimeError(msg)
+    else:
+        data = [data]
+
+    return data
+
+
+def filter_inputs_structure(
+    manifest: Manifest,
+    outdir: Path,
+    override: bool = False,
+) -> Manifest:
+    """Filter the manifest to only include missing predictions.
+
+    Parameters
+    ----------
+    manifest : Manifest
+        The manifest of the input data.
+    outdir : Path
+        The output directory.
+    override: bool
+        Whether to override existing predictions.
+
+    Returns
+    -------
+    Manifest
+        The manifest of the filtered input data.
+
+    """
+    # Check if existing predictions are found
+    existing = (outdir / "predictions").rglob("*")
+    existing = {e.name for e in existing if e.is_dir()}
+
+    # Remove them from the input data
+    if existing and not override:
+        manifest = Manifest([r for r in manifest.records if r.id not in existing])
+        msg = (
+            f"Found some existing predictions ({len(existing)}), "
+            f"skipping and running only the missing ones, "
+            "if any. If you wish to override these existing "
+            "predictions, please set the --override flag."
+        )
+        click.echo(msg)
+    elif existing and override:
+        msg = f"Found {len(existing)} existing predictions, will override."
+        click.echo(msg)
+
+    return manifest
+
+
+def filter_inputs_affinity(
+    manifest: Manifest,
+    outdir: Path,
+    override: bool = False,
+) -> Manifest:
+    """Check the input data and output directory for affinity.
+
+    Parameters
+    ----------
+    manifest : Manifest
+        The manifest.
+    outdir : Path
+        The output directory.
+    override: bool
+        Whether to override existing predictions.
+
+    Returns
+    -------
+    Manifest
+        The manifest of the filtered input data.
+
+    """
+    click.echo("Checking input data for affinity.")
+
+    # Get all affinity targets
+    existing = {
+        r.id
+        for r in manifest.records
+        if r.affinity
+        and (outdir / "predictions" / r.id / f"affinity_{r.id}.json").exists()
+    }
+
+    # Remove them from the input data
+    if existing and not override:
+        num_skipped = len(existing)
+        msg = (
+            f"Found some existing affinity predictions ({num_skipped}), "
+            f"skipping and running only the missing ones, "
+            "if any. If you wish to override these existing "
+            "affinity predictions, please set the --override flag."
+        )
+        click.echo(msg)
+    elif existing and override:
+        msg = "Found existing affinity predictions, will override."
+        click.echo(msg)
+
+    return Manifest([r for r in manifest.records if r.id not in existing])
+
+
+def compute_msa(
+    data: dict[str, str],
+    target_id: str,
+    msa_dir: Path,
+    msa_server_url: str,
+    msa_pairing_strategy: str,
+) -> None:
+    """Compute the MSA for the input data.
+
+    Parameters
+    ----------
+    data : dict[str, str]
+        The input protein sequences.
+    target_id : str
+        The target id.
+    msa_dir : Path
+        The msa directory.
+    msa_server_url : str
+        The MSA server URL.
+    msa_pairing_strategy : str
+        The MSA pairing strategy.
+
+    """
+    if len(data) > 1:
+        paired_msas = run_mmseqs2(
+            list(data.values()),
+            msa_dir / f"{target_id}_paired_tmp",
+            use_env=True,
+            use_pairing=True,
+            host_url=msa_server_url,
+            pairing_strategy=msa_pairing_strategy,
+        )
+    else:
+        paired_msas = [""] * len(data)
+
+    unpaired_msa = run_mmseqs2(
+        list(data.values()),
+        msa_dir / f"{target_id}_unpaired_tmp",
+        use_env=True,
+        use_pairing=False,
+        host_url=msa_server_url,
+        pairing_strategy=msa_pairing_strategy,
+    )
+
+    for idx, name in enumerate(data):
+        # Get paired sequences
+        paired = paired_msas[idx].strip().splitlines()
+        paired = paired[1::2]  # ignore headers
+        paired = paired[: const.max_paired_seqs]
+
+        # Set key per row and remove empty sequences
+        keys = [idx for idx, s in enumerate(paired) if s != "-" * len(s)]
+        paired = [s for s in paired if s != "-" * len(s)]
+
+        # Combine paired-unpaired sequences
+        unpaired = unpaired_msa[idx].strip().splitlines()
+        unpaired = unpaired[1::2]
+        unpaired = unpaired[: (const.max_msa_seqs - len(paired))]
+        if paired:
+            unpaired = unpaired[1:]  # ignore query is already present
+
+        # Combine
+        seqs = paired + unpaired
+        keys = keys + [-1] * len(unpaired)
+
+        # Dump MSA
+        csv_str = ["key,sequence"] + [f"{key},{seq}" for key, seq in zip(keys, seqs)]
+
+        msa_path = msa_dir / f"{name}.csv"
+        with msa_path.open("w") as f:
+            f.write("\n".join(csv_str))
+
+
+def process_input(  # noqa: C901, PLR0912, PLR0915, D103
+    path: Path,
+    ccd: dict,
+    msa_dir: Path,
+    mol_dir: Path,
+    boltz2: bool,
+    use_msa_server: bool,
+    msa_server_url: str,
+    msa_pairing_strategy: str,
+    max_msa_seqs: int,
+    processed_msa_dir: Path,
+    processed_constraints_dir: Path,
+    processed_templates_dir: Path,
+    processed_mols_dir: Path,
+    structure_dir: Path,
+    records_dir: Path,
+) -> None:
+    try:
+        # Parse data
+        if path.suffix in (".fa", ".fas", ".fasta"):
+            target = parse_fasta(path, ccd, mol_dir, boltz2)
+        elif path.suffix in (".yml", ".yaml"):
+            target = parse_yaml(path, ccd, mol_dir, boltz2)
+        elif path.is_dir():
+            msg = f"Found directory {path} instead of .fasta or .yaml, skipping."
+            raise RuntimeError(msg)  # noqa: TRY301
+        else:
+            msg = (
+                f"Unable to parse filetype {path.suffix}, "
+                "please provide a .fasta or .yaml file."
+            )
+            raise RuntimeError(msg)  # noqa: TRY301
+
+        # Get target id
+        target_id = target.record.id
+
+        # Get all MSA ids and decide whether to generate MSA
+        to_generate = {}
+        prot_id = const.chain_type_ids["PROTEIN"]
+        for chain in target.record.chains:
+            # Add to generate list, assigning entity id
+            if (chain.mol_type == prot_id) and (chain.msa_id == 0):
+                entity_id = chain.entity_id
+                msa_id = f"{target_id}_{entity_id}"
+                to_generate[msa_id] = target.sequences[entity_id]
+                chain.msa_id = msa_dir / f"{msa_id}.csv"
+
+            # We do not support msa generation for non-protein chains
+            elif chain.msa_id == 0:
+                chain.msa_id = -1
+
+        # Generate MSA
+        if to_generate and not use_msa_server:
+            msg = "Missing MSA's in input and --use_msa_server flag not set."
+            raise RuntimeError(msg)  # noqa: TRY301
+
+        if to_generate:
+            msg = f"Generating MSA for {path} with {len(to_generate)} protein entities."
+            click.echo(msg)
+            compute_msa(
+                data=to_generate,
+                target_id=target_id,
+                msa_dir=msa_dir,
+                msa_server_url=msa_server_url,
+                msa_pairing_strategy=msa_pairing_strategy,
+            )
+
+        # Parse MSA data
+        msas = sorted({c.msa_id for c in target.record.chains if c.msa_id != -1})
+        msa_id_map = {}
+        for msa_idx, msa_id in enumerate(msas):
+            # Check that raw MSA exists
+            msa_path = Path(msa_id)
+            if not msa_path.exists():
+                msg = f"MSA file {msa_path} not found."
+                raise FileNotFoundError(msg)  # noqa: TRY301
+
+            # Dump processed MSA
+            processed = processed_msa_dir / f"{target_id}_{msa_idx}.npz"
+            msa_id_map[msa_id] = f"{target_id}_{msa_idx}"
+            if not processed.exists():
+                # Parse A3M
+                if msa_path.suffix == ".a3m":
+                    msa: MSA = parse_a3m(
+                        msa_path,
+                        taxonomy=None,
+                        max_seqs=max_msa_seqs,
+                    )
+                elif msa_path.suffix == ".csv":
+                    msa: MSA = parse_csv(msa_path, max_seqs=max_msa_seqs)
+                else:
+                    msg = f"MSA file {msa_path} not supported, only a3m or csv."
+                    raise RuntimeError(msg)  # noqa: TRY301
+
+                msa.dump(processed)
+
+        # Modify records to point to processed MSA
+        for c in target.record.chains:
+            if (c.msa_id != -1) and (c.msa_id in msa_id_map):
+                c.msa_id = msa_id_map[c.msa_id]
+
+        # Dump templates
+        for template_id, template in target.templates.items():
+            name = f"{target.record.id}_{template_id}.npz"
+            template_path = processed_templates_dir / name
+            template.dump(template_path)
+
+        # Dump constraints
+        constraints_path = processed_constraints_dir / f"{target.record.id}.npz"
+        target.residue_constraints.dump(constraints_path)
+
+        # Dump extra molecules
+        Chem.SetDefaultPickleProperties(Chem.PropertyPickleOptions.AllProps)
+        with (processed_mols_dir / f"{target.record.id}.pkl").open("wb") as f:
+            pickle.dump(target.extra_mols, f)
+
+        # Dump structure
+        struct_path = structure_dir / f"{target.record.id}.npz"
+        target.structure.dump(struct_path)
+
+        # Dump record
+        record_path = records_dir / f"{target.record.id}.json"
+        target.record.dump(record_path)
+
+    except Exception as e:  # noqa: BLE001
+        import traceback
+
+        traceback.print_exc()
+        print(f"Failed to process {path}. Skipping. Error: {e}.")  # noqa: T201
+
+
+@rank_zero_only
+def process_inputs(
+    data: list[Path],
+    out_dir: Path,
+    ccd_path: Path,
+    mol_dir: Path,
+    msa_server_url: str,
+    msa_pairing_strategy: str,
+    max_msa_seqs: int = 8192,
+    use_msa_server: bool = False,
+    boltz2: bool = False,
+    preprocessing_threads: int = 1,
+) -> Manifest:
+    """Process the input data and output directory.
+
+    Parameters
+    ----------
+    data : list[Path]
+        The input data.
+    out_dir : Path
+        The output directory.
+    ccd_path : Path
+        The path to the CCD dictionary.
+    max_msa_seqs : int, optional
+        Max number of MSA sequences, by default 4096.
+    use_msa_server : bool, optional
+        Whether to use the MMSeqs2 server for MSA generation, by default False.
+    boltz2: bool, optional
+        Whether to use Boltz2, by default False.
+    preprocessing_threads: int, optional
+        The number of threads to use for preprocessing, by default 1.
+
+    Returns
+    -------
+    Manifest
+        The manifest of the processed input data.
+
+    """
+    # Check if records exist at output path
+    records_dir = out_dir / "processed" / "records"
+    if records_dir.exists():
+        # Load existing records
+        existing = [Record.load(p) for p in records_dir.glob("*.json")]
+        processed_ids = {record.id for record in existing}
+
+        # Filter to missing only
+        data = [d for d in data if d.stem not in processed_ids]
+
+        # Nothing to do, update the manifest and return
+        if data:
+            click.echo(
+                f"Found {len(existing)} existing processed inputs, skipping them."
+            )
+        else:
+            click.echo("All inputs are already processed.")
+            updated_manifest = Manifest(existing)
+            updated_manifest.dump(out_dir / "processed" / "manifest.json")
+
+    # Create output directories
+    msa_dir = out_dir / "msa"
+    records_dir = out_dir / "processed" / "records"
+    structure_dir = out_dir / "processed" / "structures"
+    processed_msa_dir = out_dir / "processed" / "msa"
+    processed_constraints_dir = out_dir / "processed" / "constraints"
+    processed_templates_dir = out_dir / "processed" / "templates"
+    processed_mols_dir = out_dir / "processed" / "mols"
+    predictions_dir = out_dir / "predictions"
+
+    out_dir.mkdir(parents=True, exist_ok=True)
+    msa_dir.mkdir(parents=True, exist_ok=True)
+    records_dir.mkdir(parents=True, exist_ok=True)
+    structure_dir.mkdir(parents=True, exist_ok=True)
+    processed_msa_dir.mkdir(parents=True, exist_ok=True)
+    processed_constraints_dir.mkdir(parents=True, exist_ok=True)
+    processed_templates_dir.mkdir(parents=True, exist_ok=True)
+    processed_mols_dir.mkdir(parents=True, exist_ok=True)
+    predictions_dir.mkdir(parents=True, exist_ok=True)
+
+    # Load CCD
+    if boltz2:
+        ccd = load_canonicals(mol_dir)
+    else:
+        with ccd_path.open("rb") as file:
+            ccd = pickle.load(file)  # noqa: S301
+
+    # Create partial function
+    process_input_partial = partial(
+        process_input,
+        ccd=ccd,
+        msa_dir=msa_dir,
+        mol_dir=mol_dir,
+        boltz2=boltz2,
+        use_msa_server=use_msa_server,
+        msa_server_url=msa_server_url,
+        msa_pairing_strategy=msa_pairing_strategy,
+        max_msa_seqs=max_msa_seqs,
+        processed_msa_dir=processed_msa_dir,
+        processed_constraints_dir=processed_constraints_dir,
+        processed_templates_dir=processed_templates_dir,
+        processed_mols_dir=processed_mols_dir,
+        structure_dir=structure_dir,
+        records_dir=records_dir,
+    )
+
+    # Parse input data
+    preprocessing_threads = min(preprocessing_threads, len(data))
+    click.echo(f"Processing {len(data)} inputs with {preprocessing_threads} threads.")
+
+    if preprocessing_threads > 1 and len(data) > 1:
+        with Pool(preprocessing_threads) as pool:
+            list(tqdm(pool.imap(process_input_partial, data), total=len(data)))
+    else:
+        for path in tqdm(data):
+            process_input_partial(path)
+
+    # Load all records and write manifest
+    records = [Record.load(p) for p in records_dir.glob("*.json")]
+    manifest = Manifest(records)
+    manifest.dump(out_dir / "processed" / "manifest.json")
+
+
+@click.group()
+def cli() -> None:
+    """Boltz."""
+    return
+
+
+@cli.command()
+@click.argument("data", type=click.Path(exists=True))
+@click.option(
+    "--out_dir",
+    type=click.Path(exists=False),
+    help="The path where to save the predictions.",
+    default="./",
+)
+@click.option(
+    "--cache",
+    type=click.Path(exists=False),
+    help=(
+        "The directory where to download the data and model. "
+        "Default is ~/.boltz, or $BOLTZ_CACHE if set."
+    ),
+    default=get_cache_path,
+)
+@click.option(
+    "--checkpoint",
+    type=click.Path(exists=True),
+    help="An optional checkpoint, will use the provided Boltz-1 model by default.",
+    default=None,
+)
+@click.option(
+    "--devices",
+    type=int,
+    help="The number of devices to use for prediction. Default is 1.",
+    default=1,
+)
+@click.option(
+    "--accelerator",
+    type=click.Choice(["gpu", "cpu", "tpu"]),
+    help="The accelerator to use for prediction. Default is gpu.",
+    default="gpu",
+)
+@click.option(
+    "--recycling_steps",
+    type=int,
+    help="The number of recycling steps to use for prediction. Default is 3.",
+    default=3,
+)
+@click.option(
+    "--sampling_steps",
+    type=int,
+    help="The number of sampling steps to use for prediction. Default is 200.",
+    default=200,
+)
+@click.option(
+    "--diffusion_samples",
+    type=int,
+    help="The number of diffusion samples to use for prediction. Default is 1.",
+    default=1,
+)
+@click.option(
+    "--max_parallel_samples",
+    type=int,
+    help="The maximum number of samples to predict in parallel. Default is None.",
+    default=5,
+)
+@click.option(
+    "--step_scale",
+    type=float,
+    help=(
+        "The step size is related to the temperature at "
+        "which the diffusion process samples the distribution. "
+        "The lower the higher the diversity among samples "
+        "(recommended between 1 and 2). "
+        "Default is 1.638 for Boltz-1 and 1.5 for Boltz-2. "
+        "If not provided, the default step size will be used."
+    ),
+    default=None,
+)
+@click.option(
+    "--write_full_pae",
+    type=bool,
+    is_flag=True,
+    help="Whether to dump the pae into a npz file. Default is True.",
+)
+@click.option(
+    "--write_full_pde",
+    type=bool,
+    is_flag=True,
+    help="Whether to dump the pde into a npz file. Default is False.",
+)
+@click.option(
+    "--output_format",
+    type=click.Choice(["pdb", "mmcif"]),
+    help="The output format to use for the predictions. Default is mmcif.",
+    default="mmcif",
+)
+@click.option(
+    "--num_workers",
+    type=int,
+    help="The number of dataloader workers to use for prediction. Default is 2.",
+    default=2,
+)
+@click.option(
+    "--override",
+    is_flag=True,
+    help="Whether to override existing found predictions. Default is False.",
+)
+@click.option(
+    "--seed",
+    type=int,
+    help="Seed to use for random number generator. Default is None (no seeding).",
+    default=None,
+)
+@click.option(
+    "--use_msa_server",
+    is_flag=True,
+    help="Whether to use the MMSeqs2 server for MSA generation. Default is False.",
+)
+@click.option(
+    "--msa_server_url",
+    type=str,
+    help="MSA server url. Used only if --use_msa_server is set. ",
+    default="https://api.colabfold.com",
+)
+@click.option(
+    "--msa_pairing_strategy",
+    type=str,
+    help=(
+        "Pairing strategy to use. Used only if --use_msa_server is set. "
+        "Options are 'greedy' and 'complete'"
+    ),
+    default="greedy",
+)
+@click.option(
+    "--use_potentials",
+    is_flag=True,
+    help="Whether to not use potentials for steering. Default is False.",
+)
+@click.option(
+    "--model",
+    default="boltz2",
+    type=click.Choice(["boltz1", "boltz2"]),
+    help="The model to use for prediction. Default is boltz2.",
+)
+@click.option(
+    "--method",
+    type=str,
+    help="The method to use for prediction. Default is None.",
+    default=None,
+)
+@click.option(
+    "--preprocessing-threads",
+    type=int,
+    help="The number of threads to use for preprocessing. Default is 1.",
+    default=multiprocessing.cpu_count(),
+)
+@click.option(
+    "--affinity_mw_correction",
+    is_flag=True,
+    type=bool,
+    help="Whether to add the Molecular Weight correction to the affinity value head.",
+)
+@click.option(
+    "--sampling_steps_affinity",
+    type=int,
+    help="The number of sampling steps to use for affinity prediction. Default is 200.",
+    default=200,
+)
+@click.option(
+    "--diffusion_samples_affinity",
+    type=int,
+    help="The number of diffusion samples to use for affinity prediction. Default is 5.",
+    default=5,
+)
+@click.option(
+    "--affinity_checkpoint",
+    type=click.Path(exists=True),
+    help="An optional checkpoint, will use the provided Boltz-1 model by default.",
+    default=None,
+)
+@click.option(
+    "--max_msa_seqs",
+    type=int,
+    help="The maximum number of MSA sequences to use for prediction. Default is 8192.",
+    default=8192,
+)
+@click.option(
+    "--subsample_msa",
+    is_flag=True,
+    help="Whether to subsample the MSA. Default is True.",
+)
+@click.option(
+    "--num_subsampled_msa",
+    type=int,
+    help="The number of MSA sequences to subsample. Default is 1024.",
+    default=1024,
+)
+@click.option(
+    "--no_kernels",
+    is_flag=True,
+    help="Whether to disable the kernels. Default False",
+)
+def predict(  # noqa: C901, PLR0915, PLR0912
+    data: str,
+    out_dir: str,
+    cache: str = "~/.boltz",
+    checkpoint: Optional[str] = None,
+    affinity_checkpoint: Optional[str] = None,
+    devices: int = 1,
+    accelerator: str = "gpu",
+    recycling_steps: int = 3,
+    sampling_steps: int = 200,
+    diffusion_samples: int = 1,
+    sampling_steps_affinity: int = 200,
+    diffusion_samples_affinity: int = 3,
+    max_parallel_samples: Optional[int] = None,
+    step_scale: Optional[float] = None,
+    write_full_pae: bool = False,
+    write_full_pde: bool = False,
+    output_format: Literal["pdb", "mmcif"] = "mmcif",
+    num_workers: int = 2,
+    override: bool = False,
+    seed: Optional[int] = None,
+    use_msa_server: bool = False,
+    msa_server_url: str = "https://api.colabfold.com",
+    msa_pairing_strategy: str = "greedy",
+    use_potentials: bool = False,
+    model: Literal["boltz1", "boltz2"] = "boltz2",
+    method: Optional[str] = None,
+    affinity_mw_correction: Optional[bool] = False,
+    preprocessing_threads: int = 1,
+    max_msa_seqs: int = 8192,
+    subsample_msa: bool = True,
+    num_subsampled_msa: int = 1024,
+    no_kernels: bool = False,
+) -> None:
+    """Run predictions with Boltz."""
+    # If cpu, write a friendly warning
+    if accelerator == "cpu":
+        msg = "Running on CPU, this will be slow. Consider using a GPU."
+        click.echo(msg)
+
+    # Supress some lightning warnings
+    warnings.filterwarnings(
+        "ignore", ".*that has Tensor Cores. To properly utilize them.*"
+    )
+
+    # Set no grad
+    torch.set_grad_enabled(False)
+
+    # Ignore matmul precision warning
+    torch.set_float32_matmul_precision("highest")
+
+    # Set rdkit pickle logic
+    Chem.SetDefaultPickleProperties(Chem.PropertyPickleOptions.AllProps)
+
+    # Set seed if desired
+    if seed is not None:
+        seed_everything(seed)
+
+    for key in ["CUEQ_DEFAULT_CONFIG", "CUEQ_DISABLE_AOT_TUNING"]:
+        # Disable kernel tuning by default,
+        # but do not modify envvar if already set by caller
+        os.environ[key] = os.environ.get(key, "1")
+
+    # Set cache path
+    cache = Path(cache).expanduser()
+    cache.mkdir(parents=True, exist_ok=True)
+
+    # Create output directories
+    data = Path(data).expanduser()
+    out_dir = Path(out_dir).expanduser()
+    out_dir = out_dir / f"boltz_results_{data.stem}"
+    out_dir.mkdir(parents=True, exist_ok=True)
+
+    # Download necessary data and model
+    if model == "boltz1":
+        download_boltz1(cache)
+    elif model == "boltz2":
+        download_boltz2(cache)
+    else:
+        msg = f"Model {model} not supported. Supported: boltz1, boltz2."
+        raise ValueError(f"Model {model} not supported.")
+
+    # Validate inputs
+    data = check_inputs(data)
+
+    # Check method
+    if method is not None:
+        if model == "boltz1":
+            msg = "Method conditioning is not supported for Boltz-1."
+            raise ValueError(msg)
+        if method.lower() not in const.method_types_ids:
+            method_names = list(const.method_types_ids.keys())
+            msg = f"Method {method} not supported. Supported: {method_names}"
+            raise ValueError(msg)
+
+    # Process inputs
+    ccd_path = cache / "ccd.pkl"
+    mol_dir = cache / "mols"
+    process_inputs(
+        data=data,
+        out_dir=out_dir,
+        ccd_path=ccd_path,
+        mol_dir=mol_dir,
+        use_msa_server=use_msa_server,
+        msa_server_url=msa_server_url,
+        msa_pairing_strategy=msa_pairing_strategy,
+        boltz2=model == "boltz2",
+        preprocessing_threads=preprocessing_threads,
+        max_msa_seqs=max_msa_seqs,
+    )
+
+    # Load manifest
+    manifest = Manifest.load(out_dir / "processed" / "manifest.json")
+
+    # Filter out existing predictions
+    filtered_manifest = filter_inputs_structure(
+        manifest=manifest,
+        outdir=out_dir,
+        override=override,
+    )
+
+    # Load processed data
+    processed_dir = out_dir / "processed"
+    processed = BoltzProcessedInput(
+        manifest=filtered_manifest,
+        targets_dir=processed_dir / "structures",
+        msa_dir=processed_dir / "msa",
+        constraints_dir=(
+            (processed_dir / "constraints")
+            if (processed_dir / "constraints").exists()
+            else None
+        ),
+        template_dir=(
+            (processed_dir / "templates")
+            if (processed_dir / "templates").exists()
+            else None
+        ),
+        extra_mols_dir=(
+            (processed_dir / "mols") if (processed_dir / "mols").exists() else None
+        ),
+    )
+
+    # Set up trainer
+    strategy = "auto"
+    if (isinstance(devices, int) and devices > 1) or (
+        isinstance(devices, list) and len(devices) > 1
+    ):
+        start_method = "fork" if platform.system() != "win32" else "spawn"
+        strategy = DDPStrategy(start_method=start_method)
+        if len(filtered_manifest.records) < devices:
+            msg = (
+                "Number of requested devices is greater "
+                "than the number of predictions, taking the minimum."
+            )
+            click.echo(msg)
+            if isinstance(devices, list):
+                devices = devices[: max(1, len(filtered_manifest.records))]
+            else:
+                devices = max(1, min(len(filtered_manifest.records), devices))
+
+    # Set up model parameters
+    if model == "boltz2":
+        diffusion_params = Boltz2DiffusionParams()
+        step_scale = 1.5 if step_scale is None else step_scale
+        diffusion_params.step_scale = step_scale
+        pairformer_args = PairformerArgsV2()
+    else:
+        diffusion_params = BoltzDiffusionParams()
+        step_scale = 1.638 if step_scale is None else step_scale
+        diffusion_params.step_scale = step_scale
+        pairformer_args = PairformerArgs()
+
+    msa_args = MSAModuleArgs(
+        subsample_msa=subsample_msa,
+        num_subsampled_msa=num_subsampled_msa,
+        use_paired_feature=model == "boltz2",
+    )
+
+    # # Create prediction writer
+    # pred_writer = BoltzWriter(
+    #     data_dir=processed.targets_dir,
+    #     output_dir=out_dir / "predictions",
+    #     output_format=output_format,
+    #     boltz2=model == "boltz2",
+    # )
+
+    # # Set up trainer
+    # trainer = Trainer(
+    #     default_root_dir=out_dir,
+    #     strategy=strategy,
+    #     callbacks=[pred_writer],
+    #     accelerator=accelerator,
+    #     devices=devices,
+    #     precision=32 if model == "boltz1" else "bf16-mixed",
+    # )
+
+    # if filtered_manifest.records:
+    #     msg = f"Running structure prediction for {len(filtered_manifest.records)} input"
+    #     msg += "s." if len(filtered_manifest.records) > 1 else "."
+    #     click.echo(msg)
+
+    #     # Create data module
+    #     if model == "boltz2":
+    #         data_module = Boltz2InferenceDataModule(
+    #             manifest=processed.manifest,
+    #             target_dir=processed.targets_dir,
+    #             msa_dir=processed.msa_dir,
+    #             mol_dir=mol_dir,
+    #             num_workers=num_workers,
+    #             constraints_dir=processed.constraints_dir,
+    #             template_dir=processed.template_dir,
+    #             extra_mols_dir=processed.extra_mols_dir,
+    #             override_method=method,
+    #         )
+    #     else:
+    #         data_module = BoltzInferenceDataModule(
+    #             manifest=processed.manifest,
+    #             target_dir=processed.targets_dir,
+    #             msa_dir=processed.msa_dir,
+    #             num_workers=num_workers,
+    #             constraints_dir=processed.constraints_dir,
+    #         )
+
+    #     # Load model
+    #     if checkpoint is None:
+    #         if model == "boltz2":
+    #             checkpoint = cache / "boltz2_conf.ckpt"
+    #         else:
+    #             checkpoint = cache / "boltz1_conf.ckpt"
+
+    #     predict_args = {
+    #         "recycling_steps": recycling_steps,
+    #         "sampling_steps": sampling_steps,
+    #         "diffusion_samples": diffusion_samples,
+    #         "max_parallel_samples": max_parallel_samples,
+    #         "write_confidence_summary": True,
+    #         "write_full_pae": write_full_pae,
+    #         "write_full_pde": write_full_pde,
+    #     }
+
+    #     steering_args = BoltzSteeringParams()
+    #     steering_args.fk_steering = use_potentials
+    #     steering_args.guidance_update = use_potentials
+
+    #     model_cls = Boltz2 if model == "boltz2" else Boltz1
+    #     model_module = model_cls.load_from_checkpoint(
+    #         checkpoint,
+    #         strict=True,
+    #         predict_args=predict_args,
+    #         map_location="cpu",
+    #         diffusion_process_args=asdict(diffusion_params),
+    #         ema=False,
+    #         use_kernels=not no_kernels,
+    #         pairformer_args=asdict(pairformer_args),
+    #         msa_args=asdict(msa_args),
+    #         steering_args=asdict(steering_args),
+    #     )
+    #     model_module.eval()
+
+    #     # Compute structure predictions
+    #     trainer.predict(
+    #         model_module,
+    #         datamodule=data_module,
+    #         return_predictions=False,
+    #     )
+
+    # Check if affinity predictions are needed
+    if any(r.affinity for r in manifest.records):
+        # Print header
+        click.echo("\nPredicting property: affinity\n")
+
+        # Validate inputs
+        manifest_filtered = filter_inputs_affinity(
+            manifest=manifest,
+            outdir=out_dir,
+            override=override,
+        )
+        if not manifest_filtered.records:
+            click.echo("Found existing affinity predictions for all inputs, skipping.")
+            return
+
+        msg = f"Running affinity prediction for {len(manifest_filtered.records)} input"
+        msg += "s." if len(manifest_filtered.records) > 1 else "."
+        click.echo(msg)
+
+        pred_writer = BoltzAffinityWriter(
+            data_dir=processed.targets_dir,
+            output_dir=out_dir / "predictions",
+        )
+
+        trainer = Trainer(
+            default_root_dir=out_dir,
+            strategy=strategy,
+            callbacks=[pred_writer],
+            accelerator=accelerator,
+            devices=devices,
+            precision=32 if model == "boltz1" else "bf16-mixed",
+        )
 
-from boltz.data.parse.sdf import parse_sdf
-from boltz.data.types import StructureV2
+        data_module = Boltz2InferenceDataModule(
+            manifest=manifest_filtered,
+            target_dir=out_dir / "predictions",
+            msa_dir=processed.msa_dir,
+            mol_dir=mol_dir,
+            num_workers=num_workers,
+            constraints_dir=processed.constraints_dir,
+            template_dir=processed.template_dir,
+            extra_mols_dir=processed.extra_mols_dir,
+            override_method="other",
+            affinity=True,
+        )
 
+        predict_affinity_args = {
+            "recycling_steps": 5,
+            "sampling_steps": sampling_steps_affinity,
+            "diffusion_samples": diffusion_samples_affinity,
+            "max_parallel_samples": 1,
+            "write_confidence_summary": False,
+            "write_full_pae": False,
+            "write_full_pde": False,
+        }
 
-def main():
-    parser = argparse.ArgumentParser(description="Convert SDF to Boltz pre_affinity_*.npz format.")
-    parser.add_argument('--sdf', type=str, required=True, help='Input SDF file (protein-ligand complex)')
-    parser.add_argument('--ligand_id', type=str, required=True, help='Ligand ID (used in output filename)')
-    parser.add_argument('--output', type=str, required=True, help='Output .npz file path')
-    args = parser.parse_args()
+        # Load affinity model
+        if affinity_checkpoint is None:
+            affinity_checkpoint = cache / "boltz2_aff.ckpt"
 
-    sdf_path = Path(args.sdf)
-    output_path = Path(args.output)
+        model_module = Boltz2.load_from_checkpoint(
+            affinity_checkpoint,
+            strict=True,
+            predict_args=predict_affinity_args,
+            map_location="cpu",
+            diffusion_process_args=asdict(diffusion_params),
+            ema=False,
+            pairformer_args=asdict(pairformer_args),
+            msa_args=asdict(msa_args),
+            steering_args={"fk_steering": False, "guidance_update": False},
+            affinity_mw_correction=affinity_mw_correction,
+        )
+        model_module.eval()
 
-    # Parse the SDF file to StructureV2
-    structure: StructureV2 = parse_sdf(sdf_path)
+        trainer.callbacks[0] = pred_writer
+        trainer.predict(
+            model_module,
+            datamodule=data_module,
+            return_predictions=False,
+        )
 
-    # Save as pre_affinity_[ligand_id].npz
-    structure.dump(output_path)
-    print(f"Saved: {output_path}")
 
 if __name__ == "__main__":
-    main() 
+    cli()

{boltz_vsynthes-0.0.12.dist-info → boltz_vsynthes-0.0.14.dist-info}/METADATA

@@ -1,6 +1,6 @@
 Metadata-Version: 2.4
 Name: boltz-vsynthes
-Version: 0.0.12
+Version: 0.0.14
 Summary: Boltz for VSYNTHES
 Requires-Python: <3.13,>=3.10
 Description-Content-Type: text/markdown

{boltz_vsynthes-0.0.12.dist-info → boltz_vsynthes-0.0.14.dist-info}/RECORD

@@ -108,11 +108,11 @@ boltz/model/potentials/__init__.py,sha256=47DEQpj8HBSa-_TImW-5JCeuQeRkm5NMpJWZG3
 boltz/model/potentials/potentials.py,sha256=vev8Vjfs-ML1hyrdv_R8DynG4wSFahJ6nzPWp7CYQqw,17507
 boltz/model/potentials/schedules.py,sha256=m7XJjfuF9uTX3bR9VisXv1rvzJjxiD8PobXRpcBBu1c,968
 boltz/utils/sdf_splitter.py,sha256=ZHn_syOcmm-fDnJ3YEGyGv_vYz2IRzUW7vbbMSU2JBY,2108
-boltz/utils/sdf_to_pre_affinity_npz.py,sha256=ev0s2pS8NoB-_3BkSjRKk3GMnqjOxTRCH-r9avKYGOg,1212
+boltz/utils/sdf_to_pre_affinity_npz.py,sha256=ro0KGe24JexbJm47J8S8w8Lmr_KaQbzOAb_dKZO2G9I,40384
 boltz/utils/yaml_generator.py,sha256=ermWIG-BE6nNWHFvpEwpk92N9J-YATpGXZGLvD1I2oQ,4012
-boltz_vsynthes-0.0.12.dist-info/licenses/LICENSE,sha256=8GZ_1eZsUeG6jdqgJJxtciWzADfgLEV4LY8sKUOsJhc,1102
-boltz_vsynthes-0.0.12.dist-info/METADATA,sha256=XPcHZExavOK9oz8BaZnp31f-acFOXbCKwmDORbDxaP8,7235
-boltz_vsynthes-0.0.12.dist-info/WHEEL,sha256=_zCd3N1l69ArxyTb8rzEoP9TpbYXkqRFSNOD5OuxnTs,91
-boltz_vsynthes-0.0.12.dist-info/entry_points.txt,sha256=WlXNdHTJF1ahGN-H1QpgMbZm_5SobXY05eiuT8buycw,212
-boltz_vsynthes-0.0.12.dist-info/top_level.txt,sha256=MgU3Jfb-ctWm07YGMts68PMjSh9v26D0gfG3dFRmVFA,6
-boltz_vsynthes-0.0.12.dist-info/RECORD,,
+boltz_vsynthes-0.0.14.dist-info/licenses/LICENSE,sha256=8GZ_1eZsUeG6jdqgJJxtciWzADfgLEV4LY8sKUOsJhc,1102
+boltz_vsynthes-0.0.14.dist-info/METADATA,sha256=hopmZgbr8M8tfFZ3kjGbeYSNvIldCDN1qkNEN4v8ePY,7235
+boltz_vsynthes-0.0.14.dist-info/WHEEL,sha256=_zCd3N1l69ArxyTb8rzEoP9TpbYXkqRFSNOD5OuxnTs,91
+boltz_vsynthes-0.0.14.dist-info/entry_points.txt,sha256=nZNYPKKrmAr-MVA0K-ClNRT2p90FV1_14d7HpsESZFQ,211
+boltz_vsynthes-0.0.14.dist-info/top_level.txt,sha256=MgU3Jfb-ctWm07YGMts68PMjSh9v26D0gfG3dFRmVFA,6
+boltz_vsynthes-0.0.14.dist-info/RECORD,,

{boltz_vsynthes-0.0.12.dist-info → boltz_vsynthes-0.0.14.dist-info}/entry_points.txt

@@ -1,5 +1,5 @@
 [console_scripts]
 boltz = boltz.main:cli
 boltz-generate-yaml = boltz.utils.yaml_generator:main
-boltz-sdf-to-pre-affinity = boltz.utils.sdf_to_pre_affinity_npz:main
+boltz-sdf-to-pre-affinity = boltz.utils.sdf_to_pre_affinity_npz:cli
 boltz-split-sdf = boltz.utils.sdf_splitter:main