Hi Rintarou,

On Tue, Feb 7, 2017 at 6:23 AM, Suzuki, Rintarou <rsuz...@affrc.go.jp>
wrote:

> Dear All,
>
> I'm generating conformation of a molecule:
>
> C1C2C3OC3C1C13OC21C1CC3C2OC21
>
>
> This molecule has many chiral centers and 10 possible isomers.
>
> EmbedMolecule command of RDKit_2015_03_1 can generate every isomer but
> RDKit_2016_09_3 fails in 9 of 10.
>

There are two things going on here.

In the first case:


> For example,
>
> RDKit_2015_03_1
> ---------------------------------
> >>> mol=Chem.MolFromSmiles('C1[C@H]2[C@@H]3O[C@@H]3[C@@H]1[C@@]13O[C@
> @]21[C@@H]1C[C@H]3[C@@H]2O[C@@H]21')
> >>> Chem.FindMolChiralCenters( copy(m), includeUnassigned=True )
>
> [(1, 'S'), (2, 'S'), (4, 'R'), (5, 'R'), (6, 'R'), (8, 'R'), (9, 'R'),
> (11, 'S'), (12, 'S'), (14, 'R')]
>
> >>> m=Chem.AddHs(mol)
> >>> AllChem.EmbedMolecule( m, randomSeed = 256, maxAttempts = 1,
> clearConfs = False )
>
> 0
> ---------------------------------
>
>
> RDKit_2016_09_3
> ---------------------------------
> >>> mol=Chem.MolFromSmiles('C1[C@H]2[C@@H]3O[C@@H]3[C@@H]1[C@@]13O[C@
> @]21[C@@H]1C[C@H]3[C@@H]2O[C@@H]21')
> >>> m=Chem.AddHs(mol)
> >>> Chem.FindMolChiralCenters( copy(m), includeUnassigned=True )
>
> [(1, 'S'), (2, 'S'), (4, 'R'), (5, 'R'), (6, 'R'), (8, 'R'), (9, 'R'),
> (11, 'S'), (12, 'S'), (14, 'R')]
>
> >>> AllChem.EmbedMolecule( m, randomSeed = 256, maxAttempts = 100,
> clearConfs = False )
>
> -1
>

I will need to check, but this is likely due to one of the checks added in
the last release that was designed to prevent ugly structures in systems
like this one. It looks like those checks are a bit too strict and need to
be made more flexible (or, likely better, you should be able to turn them
off) I'll add something for that. Thanks for reporting the problem.

---------------------------------
>
>
> Two chiral centers in this molecule are stereo-dependent (6th and 8th
> atoms).
> Conformation of molecule without assignment for these atoms can be
> generated, but the chiralities remain unassigned.
>
> RDKit_2016_09_3
> ---------------------------------
> >>> mol=Chem.MolFromSmiles('C1[C@H]2[C@@H]3O[C@@H]3[C@@H]1C13OC21[C@
> @H]1C[C@H]3[C@@H]2O[C@@H]21')
> >>> Chem.FindMolChiralCenters( copy(m), includeUnassigned=True )
>
> [(1, 'S'), (2, 'S'), (4, 'R'), (5, 'R'), (6, '?'), (8, '?'), (9, 'R'),
> (11, 'S'), (12, 'S'), (14, 'R')]
>
> >>> m=Chem.AddHs(mol)
> >>> AllChem.EmbedMolecule( m, randomSeed = 256, maxAttempts = 100,
> clearConfs = False )
>
> 0
>
> >>> Chem.AssignAtomChiralTagsFromStructure(m)
> >>> Chem.FindMolChiralCenters( copy(m), includeUnassigned=True )
>
> [(1, 'S'), (2, 'S'), (4, 'R'), (5, 'R'), (6, '?'), (8, '?'), (9, 'S'),
> (11, 'R'), (12, 'S'), (14, 'R')]
>
> >>> opt = AllChem.UFFOptimizeMolecule( m, maxIters = 10000, confId=0)
> >>> ff = AllChem.UFFGetMoleculeForceField( m, confId = 0 )
> >>> ff.Minimize()
>
> 0
>
> >>> Chem.AssignAtomChiralTagsFromStructure(m)
> >>> Chem.FindMolChiralCenters( copy(m), includeUnassigned=True )
>
> [(1, 'S'), (2, 'S'), (4, 'R'), (5, 'R'), (6, '?'), (8, '?'), (9, 'R'),
> (11, 'S'), (12, 'S'), (14, 'R')]
> ---------------------------------
>
> How can I assign chiralities of these atoms in RDKit_2016_09_3?
>

I believe that the current behavior is correct. Atoms 6 and 8 are not
chiral due to the dependent stereochemistry. What would you expect to
happen?

-greg
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