Topology.from_pdb is extremely slow on solvated protein with rdkit> 2024.09.6

[fjclark]

Describe the bug

Topology.from_pdb is extremely slow (~ 4 minutes for the example) for solvated proteins with rdkit>2024.09.6, and is relatively fast (~ 10 seconds for the example) with rdkit==2024.09.6.

This is really an RDKit issue (and I will try to raise there when I get time and investigate a bit more) but thought I'd raise here in case it affects pinning RDKit versions/ there were work-arounds.

To Reproduce
from_pdb_issue.tar.gz

Run run_reproduce.sh.

Output

=== rdkit-2024 ===
openff-toolkit 0.19.0, rdkit 2024.09.6
from_pdb took 7.38 s (26111 atoms)
=== rdkit-latest ===
openff-toolkit 0.19.0, rdkit 2026.03.6
from_pdb took 252.26 s (26111 atoms)

Computing environment:

• Ubuntu 22.04
• See pixi lock file

Additional context
The affects the workshop.

[j-wags]

Thanks for the report! Was hoping to have pablo swapped in as the backend for Topology.from_pdb by now (which I think will resolve this) but personnel shortages have pushed everything back :-/

[fjclark]

Ah great, looking forward to having that swapped in!