Two-step replacements¶

mutate_mol, grow_mol, and link_mols do two things at once: they query the database for matching fragments and then assemble the products. CReM also exposes these two steps separately:

• get_replacements — query the database and return the matching fragments.
• get_mols_from_replacements — assemble products from a set of replacements.

This is useful when you want to inspect, cache, or filter the candidate fragments before building molecules, or build products from the same replacement set more than once.

Inspect matching fragments¶

By default get_replacements yields the SMILES of the candidate replacement fragments:

from rdkit import Chem
from crem.crem import get_replacements

m = Chem.MolFromSmiles("c1cc(OC)ccc1C")
frags = list(get_replacements(m, db_name="fragments.db", radius=3, max_size=1))
print(frags[:10])

Get replacements, then build molecules¶

Set return_frag_smi_only=False to get full replacement tuples (source_core_smi, replacement_core_smi, freq, context_mol), then pass them to get_mols_from_replacements:

from rdkit import Chem
from crem.crem import get_replacements, get_mols_from_replacements

m = Chem.MolFromSmiles("c1cc(OC)ccc1C")
radius = 3

replacements = list(get_replacements(
    m,
    db_name="fragments.db",
    radius=radius,
    max_size=1,
    return_frag_smi_only=False,
))

# (optionally inspect / filter `replacements` here)

mols = list(get_mols_from_replacements(
    m,
    radius=radius,
    replacements=replacements,
    return_rxn=True,
))
# each item: [smiles, rxn]

The radius passed to get_mols_from_replacements must match the one used to fetch the replacements.

Linking¶

To search for linking fragments, pass a second molecule as mol2 to get_replacements, and the same mol2 to get_mols_from_replacements:

m1 = Chem.MolFromSmiles("c1cc(OC)ccc1C")
m2 = Chem.MolFromSmiles("NCC(=O)O")

replacements = list(get_replacements(
    m1, db_name="fragments.db", radius=3, mol2=m2,
    min_atoms=1, max_atoms=3, return_frag_smi_only=False,
))
mols = list(get_mols_from_replacements(m1, radius=3, replacements=replacements, mol2=m2))

See crem.crem for the full signatures.