Make cycle¶

make_cycle forms a new ring by connecting two atoms of the same molecule with a two-attachment-point fragment from the database. It covers both macrocyclization and the closure of smaller native rings.

from rdkit import Chem
from crem.crem import make_cycle

m = Chem.MolFromSmiles("c1ccccc1N")
res = list(make_cycle(
    m,
    db_name="fragments.db",
    radius=3,
    ring_size=(5, 7),
    min_atoms=1,
    max_atoms=10,
    replace_ids=[1, 2],
))

make_cycle works on an H-expanded copy of the molecule internally.

Two modes¶

The ring_closures argument selects which database rows are queried:

ring_closures=True (default)¶

Strict. Only ring-closure (arc-cut) fragments are queried — rows with is_ring_closure = 1. Useful for closing native, typically aliphatic rings. Requires a database built so that ring-closure rows exist: cremdb_create --frag-mode with ring, both, ring_optimal, or both_optimal. If the database has no such rows, the call raises a clear error.

ring_closures=False¶

Broad. Any linker fragment may be used; the is_ring_closure provenance is not filtered. This may be useful for transplanting intact aromatic or scaffold rings, since the donor fragment's own ring closures are preserved. This can also create macrocycles.

# Broad mode: any linker fragment
res = list(make_cycle(m, db_name="fragments.db", ring_closures=False,
                      ring_size=(5, 7), max_atoms=10))

Key parameters¶

Parameter	Meaning
ring_size	Size of the new ring (atoms = bonds). int for a single size, (min, max) for a window, None for no constraint. Translated per anchor pair into a dist2 filter as ring_size − d_in, where d_in is the topological distance between the two anchor atoms in the input molecule.
ring_closures	Which provenance to query (see above). Default True.
min_atoms / max_atoms	Heavy-atom size window of the linking fragment. Defaults 1 / 10.
replace_ids / protected_ids	Restrict which atoms may serve as ring-closure anchors.
set_names / min_freq	Fragment set and frequency threshold.

symmetry_fixes is accepted for API compatibility with the other generation functions but is not used by make_cycle.

Prefer acyclic attachment points¶

When forming rings you often want the linker to attach to acyclic atoms rather than to atoms already inside a ring. The built-in crem.utils.filter_acyclic_attachment_points filter enforces this:

from crem.utils import filter_acyclic_attachment_points

res = list(make_cycle(
    m,
    db_name="fragments.db",
    radius=3,
    ring_size=(5, 7),
    max_atoms=10,
    replace_ids=[1, 2],
    filter_func=filter_acyclic_attachment_points,
))

Parallel use¶

For multiprocessing, use the list-returning wrapper make_cycle2 — see Multiprocessing.