Calling MurckoScaffold on molecule causes bug in pickling

[dangthatsright]

Describe the bug
Calling MurckoScaffold on an rdkit mol mutates it in a way that probably has bad downstream effects. I am not entirely sure what is wrong but seems like the mol is unable to be pickled.

To Reproduce

from multiprocessing import Pool
from rdkit import Chem
from rdkit.Chem.Scaffolds import MurckoScaffold
from rdkit import DataStructs

Chem.SetDefaultPickleProperties(Chem.PropertyPickleOptions.AllProps)

def no_op(m):
    return m

mols = [Chem.MolFromSmiles(s) for s in ["C","CC"]]
# scaffolds = [MurckoScaffold.GetScaffoldForMol(m) for m in mols]

with Pool(processes=4) as pool:
    res_list = [pool.apply_async(no_op, (m,)) for m in mols]
    output = [res.get(timeout=1) for res in res_list]
    print(output)

The above code should work, but once you uncomment the MurckoScaffold section, there is a lot of pickling errors.
which looks like

Traceback (most recent call last):
  File "/home/ubuntu/miniconda/envs/lib/python3.9/multiprocessing/process.py", line 315, in _bootstrap
    self.run()
  File "/home/ubuntu/miniconda/envs/lib/python3.9/multiprocessing/process.py", line 108, in run
    self._target(*self._args, **self._kwargs)
  File "/home/ubuntu/miniconda/envs/lib/python3.9/multiprocessing/pool.py", line 114, in worker
    task = get()
  File "/home/ubuntu/miniconda/envs/lib/python3.9/multiprocessing/queues.py", line 368, in get
    return _ForkingPickler.loads(res)
ValueError: invalid BitVect pickle

Expected behavior
MurckoScaffold.GetScaffoldForMol should have no affect on the underly mol

Screenshots
If applicable, add screenshots to help explain your problem.

Configuration (please complete the following information):

• RDKit version: 2022.9.1
• OS: Ubuntu 20.04.5
• Python version (if relevant): 3.9.10
• Are you using conda? no
• If you are using conda, which channel did you install the rdkit from?
• If you are not using conda: how did you install the RDKit? pip install rdkit==2022.9.1

Additional context
Add any other context about the problem here.

[greglandrum]

@dangthatsright I cannot reproduce the error from your script

Also this isn't directly a problem with the pickling code, at least not for me:

In [20]: mols = [Chem.MolFromSmiles(s) for s in ["C","CC"]]
    ...: scaffolds = [MurckoScaffold.GetScaffoldForMol(m) for m in mols]
    ...: 
    ...: 

In [21]: pickle.loads(pickle.dumps(mols))
Out[21]: 
[<rdkit.Chem.rdchem.Mol at 0x7f1501411e90>,
 <rdkit.Chem.rdchem.Mol at 0x7f1501413ab0>]

In [22]: pickle.loads(pickle.dumps(scaffolds))
Out[22]: 
[<rdkit.Chem.rdchem.Mol at 0x7f14fbe53600>,
 <rdkit.Chem.rdchem.Mol at 0x7f14fbe5b970>]

Are you sure that there's not something else going on in the script that's causing the problem?

[dangthatsright]

@greglandrum yes you are right, I had some other imports in my script that I thought were unrelated but I was able to fully reproduce after including Chem.SetDefaultPickleProperties(Chem.PropertyPickleOptions.AllProps). I've corrected the original post

[greglandrum]

@dangthatsright that updated version still runs fine for me.
Do you get the error you report when you run exactly that script?

[dangthatsright]

Yes I get the error when I run the exact script. Are you testing on ubuntu or mac? I know multiprocessing recently changed for mac vs ubuntu so perhaps the issue is there?

[greglandrum]

Yeah, I ran it on ubuntu 22.04.

[greglandrum]

One possible difference is that I'm using the conda version of the RDKit.

[dangthatsright]

Ah maybe that's it? In any case, it doesn't matter too much for me since I just make copies of the molecule before calling MurckoScaffold. It seems like this is probably less of an issue than it's worth to fix so I'm just going to close it. Thanks for looking into it though!

[rubbs14]

Just joining in to report the same issue with the pip version of RDKit on RHL (2022.9.4)
I have the exact same error reported here after retrieving the molecules from the queue (invalid BitVect).
I am computing multiple fingerprints for each molecule with multiprocessing.

I can share the code if needed, but it is indeed very similar to @dangthatsright code

[bp-kelley]

This looks pretty nasty, but I think it's worth investigating so I'm going to keep it open. Here is a non-multiprocessing reproducible:

from rdkit import Chem                                                                                                                 
from rdkit.Chem.Scaffolds import MurckoScaffold                                                                                        
import pickle                                                                                                                          
Chem.SetDefaultPickleProperties(Chem.PropertyPickleOptions.AllProps)                                                                   
mols = [Chem.MolFromSmiles(s) for s in ["C","CC"]]                                                                                     
scaffolds = [MurckoScaffold.GetScaffoldForMol(m) for m in mols]                                                                        
[pickle.loads(pickle.dumps(m)) for m in mols]

[bp-kelley]

@greglandrum this was fun, I have a solution and it wasn't really related to the BitVector. I'll put in a PR tonight.