Hi Greg (et al.),
Thanks for looking into it.
And thanks to Paolo, who gave me a good workaround suggestion – which was to
desymmetrise the spirocyclic centre by modifying the isotope on one of the
neighbours.
This is good for attended processing of single molecules, but not so good for
unattended processing of unknown molecules…
Reading in molecules with sanitize=False is a good start, but my first thought
was then to do some sort of rSMARTS transform to automate the isomer assignment.
It soon became apparent that this wasn’t the way to go – as abilities are
limited with an unsanitised molecule(!).
So I ended-up with the following:
m3 = Chem.MolFromSmiles('O[C@H]1CC[C@]11CC[C@@](Cl)(Br)CC1', sanitize=False)
for atom in m3.GetAtoms():
print "Stereo:", atom.GetChiralTag(), "Neighbours:", [n.GetSymbol() for n
in atom.GetNeighbors()] # chiral centres currently intact
# Find possible spirocentres
for atom in m3.GetAtoms():
if len(atom.GetNeighbors()) == 4 and atom.IsInRing() and
atom.GetChiralTag() != 'CHI_UNSPECIFIED':
# We have found a candidate spirocentre modify a neighbour at random
first_neighbour = atom.GetNeighbors()[0]
first_neighbour.SetIsotope(100)
Chem.SanitizeMol(m3) # Now we can sanitise
test3_mols = summarise_conformers(m3) # and generate the conformers (as before)
sdf = Chem.SDWriter('test3.sdf') # and write them out (but resetting the
isotopes first)
for mol in test3_mols:
for atom in mol.GetAtoms():
if atom.GetIsotope() == 100:
atom.SetIsotope(0)
sdf.write(mol)
GIST is updated to include this:
https://gist.github.com/jepdavidson/fdfbf6366a17f4829de3d4de22f3b442
Kind regards
James
From: Greg Landrum [mailto:greg.land...@gmail.com]
Sent: 08 February 2017 03:45
To: James Davidson
Cc: rdkit-discuss@lists.sourceforge.net
Subject: Re: [Rdkit-discuss] Stereochemistry issue for spirocycles/pseudochiral
centres(?)
Hi James,
This is definitely a bug. The problem seems to be connected to the way what the
RDKit calls "ring stereochemistry" is handled when there are spiro linkages.
Here's the github issue: https://github.com/rdkit/rdkit/issues/1294
I'll take a look.
Best,
-greg
On Tue, Feb 7, 2017 at 8:32 PM, James Davidson
<j.david...@vernalis.com<mailto:j.david...@vernalis.com>> wrote:
Dear All,
I have hit what I think is a problem with stereochemistry perception/handling
for certain types of pseudochiral and/or spirocyclic systems.
Basically I am observing that some types of input tetrahedral stereochemical
information gets lost when an RDKit molecule is generated.
But I only realised this because I was wanting to generate conformers and was
seeing stereochemical scrambling…
Anyway, an example with pictures will probably explain things better:
https://gist.github.com/jepdavidson/fdfbf6366a17f4829de3d4de22f3b442
Any help/advice appreciated.
Kind regards
James
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