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Initial support for 3D conformer loading #40

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Initial support for 3D conformer loading #40

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14 changes: 6 additions & 8 deletions src/boltz/data/parse/fasta.py
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Original file line number Diff line number Diff line change
Expand Up @@ -66,13 +66,10 @@ def parse_fasta(path: Path, ccd: Mapping[str, Mol]) -> Target: # noqa: C901
# Get chain id, entity type and sequence
header = seq_record.id.split("|")
chain_id, entity_type = header[:2]
if len(header) == 3 and header[2] != "":
assert (
entity_type.lower() == "protein"
), "MSA_ID is only allowed for proteins"
msa_id = header[2]
if len(header) == 3:
supp_file = header[2]
else:
msa_id = None
supp_file = None

entity_type = entity_type.upper()
seq = str(seq_record.seq)
Expand All @@ -83,7 +80,7 @@ def parse_fasta(path: Path, ccd: Mapping[str, Mol]) -> Target: # noqa: C901
"id": chain_id,
"sequence": seq,
"modifications": [],
"msa": msa_id,
"msa": supp_file if len(header) == 3 else None,
},
}
elif entity_type == "RNA":
Expand Down Expand Up @@ -114,9 +111,10 @@ def parse_fasta(path: Path, ccd: Mapping[str, Mol]) -> Target: # noqa: C901
"ligand": {
"id": chain_id,
"smiles": seq,
"conformer": supp_file if len(header) == 3 else None,
}
}

sequences.append(molecule)

data = {
Expand Down
82 changes: 77 additions & 5 deletions src/boltz/data/parse/schema.py
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Original file line number Diff line number Diff line change
Expand Up @@ -7,6 +7,7 @@
from rdkit import rdBase
from rdkit.Chem import AllChem
from rdkit.Chem.rdchem import Conformer, Mol
from rdkit.Chem import SDMolSupplier, MolFromMol2File, MolFromPDBFile

from boltz.data import const
from boltz.data.types import (
Expand Down Expand Up @@ -179,7 +180,7 @@ def get_conformer(mol: Mol) -> Conformer:
# Fallback to the ideal coordinates
for c in mol.GetConformers():
try:
if c.GetProp("name") == "Ideal":
if c.GetProp("name") in ["Ideal", "File"]:
return c
except KeyError: # noqa: PERF203
pass
Expand Down Expand Up @@ -446,6 +447,63 @@ def parse_polymer(
)


def parse_conformer_file(path: str) -> None:
"""Parse a conformer file and add it to the molecule.

Parameters
----------
path : str
The path to the conformer file.
mol : Mol
The molecule to add the conformer to.

"""
if path.endswith('.sdf'):
supplier = SDMolSupplier(path)
mol = next(supplier)

elif path.endswith('.mol2'):
mol = MolFromMol2File(path)
if mol is None:
msg = f"Failed to read conformer from file: {path}"
raise ValueError(msg)

elif path.endswith('.pdb'):
mol = MolFromPDBFile(path)
if mol is None:
msg = f"Failed to read conformer from file: {path}"
raise ValueError(msg)
else:
msg = f"Unsupported conformer file format: {path}"
raise ValueError(msg)
for conf in mol.GetConformers():
conf.SetProp("name", "File")
return mol

def align_conf_to_mol(mol: Mol, conf_mol: Mol) -> None:
"""Align a conformer to a molecule.

Parameters
----------
mol : Mol
The molecule to align to.
conf_mol : Mol
The conformer to align.

"""
if not mol.HasSubstructMatch(conf_mol):
msg = "Conformer does not match molecule!"
raise ValueError(msg)
match = mol.GetSubstructMatch(conf_mol)
for idx, atom in enumerate(conf_mol.GetAtoms()):
smiles_atom = mol.GetAtomWithIdx(match[idx])
assert atom.GetProp("name") == smiles_atom.GetProp("name")
atom.SetFormalCharge(smiles_atom.GetFormalCharge()) # Transfer formal charges
atom.SetProp("name", smiles_atom.GetProp("name")) # Transfer atom names
atom.SetAtomicNum(smiles_atom.GetAtomicNum()) # Transfer atomic numbers



def parse_boltz_schema( # noqa: C901, PLR0915, PLR0912
name: str,
schema: dict,
Expand All @@ -471,6 +529,7 @@ def parse_boltz_schema( # noqa: C901, PLR0915, PLR0912
- ligand:
id: E
smiles: "CC1=CC=CC=C1"
conformer: path/to/conformer.sdf # Optional
- ligand:
id: [F, G]
ccd: []
Expand Down Expand Up @@ -519,12 +578,15 @@ def parse_boltz_schema( # noqa: C901, PLR0915, PLR0912
if entity_type in {"protein", "dna", "rna"}:
seq = str(item[entity_type]["sequence"])
elif entity_type == "ligand":
assert "smiles" in item[entity_type] or "ccd" in item[entity_type]
assert "smiles" not in item[entity_type] or "ccd" not in item[entity_type]
assert "smiles" in item[entity_type] or "ccd" in item[entity_type]
if "smiles" in item[entity_type]:
seq = str(item[entity_type]["smiles"])
else:
elif "ccd" in item[entity_type]:
seq = str(item[entity_type]["ccd"])
else:
msg = f"Invalid ligand type: {item[entity_type]}"
raise ValueError(msg)

items_to_group.setdefault((entity_type, seq), []).append(item)

# Go through entities and parse them
Expand Down Expand Up @@ -643,11 +705,21 @@ def parse_boltz_schema( # noqa: C901, PLR0915, PLR0912
canonical_order = AllChem.CanonicalRankAtoms(mol)
for atom, can_idx in zip(mol.GetAtoms(), canonical_order):
atom.SetProp("name", atom.GetSymbol().upper() + str(can_idx + 1))

success = compute_3d_conformer(mol)
if not success:
msg = f"Failed to compute 3D conformer for {seq}"
raise ValueError(msg)
if "conformer" in items[0][entity_type] and items[0][entity_type]["conformer"] is not None:
conf_mol = parse_conformer_file(items[0][entity_type]["conformer"])
conf_mol = AllChem.AddHs(conf_mol)
can_order = AllChem.CanonicalRankAtoms(conf_mol)
for atom, can_idx in zip(conf_mol.GetAtoms(), can_order):
atom.SetProp("name", atom.GetSymbol().upper() + str(can_idx + 1))
#align conformer to mol, set the metadata:
align_conf_to_mol(mol, conf_mol)
#replace the computed conformer with the one from the file

mol = conf_mol

mol_no_h = AllChem.RemoveHs(mol)
residue = parse_ccd_residue(
Expand Down