Fingerprinting functions should call assignStereochemistry() when necessary

[bricehoff]

Description:

• RDKit Version: '2018.03.2'
• Platform: Linux

There seems to be a problem with EnumerateStereoisomers or GetMorganFingerprintAsBitVect and useChirality = True. Below is an example of the issue. I was expecting fp1 and fp2 to be different in the first case. Is it a bug or am I missing something ?
Cheers,
Brice

from rdkit import Chem
from rdkit.Chem.EnumerateStereoisomers import EnumerateStereoisomers
m = Chem.MolFromSmiles('BrC=CC1OC(C2)(F)C2(Cl)C1')
isomers = tuple(EnumerateStereoisomers(m))

fp1=AllChem.GetMorganFingerprintAsBitVect(isomers[0], 4, 2048, useChirality=True)
fp2=AllChem.GetMorganFingerprintAsBitVect(isomers[1], 4, 2048, useChirality=True)
print(DataStructs.FingerprintSimilarity(fp1,fp2))
>>> 1.0

fp1=AllChem.GetMorganFingerprintAsBitVect(Chem.MolFromSmiles(Chem.MolToSmiles(isomers[0])), 4, 2048, useChirality=True)
fp2=AllChem.GetMorganFingerprintAsBitVect(Chem.MolFromSmiles(Chem.MolToSmiles(isomers[1])), 4, 2048, useChirality=True)
print(DataStructs.FingerprintSimilarity(fp1,fp2))
>>> 0.5609756097560976

[greglandrum]

Hi Brice,
What's going on here is that EnumerateStereoisomers() produces molecules with the correct configuration, but it does not (re)generate the CIP labels that the Morgan fingerprinting code uses when you ask for chirality to be used in the fingerprinting. You need to call AssignStereochemistry() in order to make things work.
We can pretty easily get rid of this opportunity for you to get the wrong results in the next major release, but in the meantime all you need to do is the following:
for isomer in isomers: Chem.AssignStereochemistry(isomer,force=True,cleanIt=True)

[bricehoff]

thanks !