rdkit-discuss

[Rdkit-discuss] Generation of stereo-isomers

[Soren W. <soe...@gm...>]

Hi,

is it possible with RDKit to generate all stereoisomers of a given compound?

If not, is anyone working on it?

If not, how difficult would it be / what would be the best way to implement
such a function.

best regards

Soren

Re: [Rdkit-discuss] Generation of stereo-isomers

[Greg L. <gre...@gm...>]

Hi Soren,

That functionality isn't currently there, but it's been requested a few
times and shouldn't be that tough to get into the next release.

-greg

On Thursday, September 24, 2015, Soren Wacker <soe...@gm...> wrote:

> Hi,
>
> is it possible with RDKit to generate all stereoisomers of a given
> compound?
>
> If not, is anyone working on it?
>
> If not, how difficult would it be / what would be the best way to
> implement such a function.
>
> best regards
>
> Soren
>

Re: [Rdkit-discuss] Generation of stereo-isomers

[Peter S. <sh...@gm...>]

Umm... would that be all stereoisomers or all realizable stereoisomers? For
example consider two bridgeheads in a norbonane-type compound. In this
case, only a particular enantiomeric pair would be realizable, and not all
four diastereomers.

Re: [Rdkit-discuss] Generation of stereo-isomers

[Paolo T. <pao...@un...>]

Dear Soren,

I have recently used the RDKit to enumerate stereocentres.
The approach I followed was to generate a 3D structure for the molecule 
of interest (including hydrogens) using EmbedMolecule(), followed by 
MMFF optimization; do not pay attention to stereochemistry at this 
stage. Then I used FindMolChiralCenters() to find the n chiral centres 
in the 3D structure thus obtained; there are 2^n theoretical possible 
diastereomers. You may enumerate all of them with a "for i in range (0, 
2^n)" loop; converting i to binary, and considering 0 for S and 1 for R, 
you may easily find all possible combinations. Use SetChiralTag() to set 
the chirality on each stereocentre, then rebuild 3D coordinates with 
EmbedMolecule() followed by MMFF optimization. Carry out a final check 
to verify that the chirality of the molecule is the one you initially 
required; if not, try to rebuild 3D coordinates. If you fail, say, 20 
times in a row, it means you are attempting to build a diastereomer that 
cannot give rise to a sensible 3D geometry (such as the case mentioned 
by Peter); then give up.
You will also need to check if any of the structures that you obtain 
during the enumeration has more chiral centres than the initial one (for 
which you didn't specify steeochemistry); in fact, it could be that you 
started from a meso structure. If this happens, just restart enumeration 
from scratch with the increased number of stereocentres.
I also carried out some geometry checks on the generated stereocentres 
coupled with MMFF energy evaluation relative to the most stable 
diastereomer to make sure that the diastereomers obtained where 
reasonable and not unreasonably strained.
This brute-force enumeration is easy to implement, reasonably fast, and 
it worked very well for me.

Kind regards,
Paolo

On 24/09/2015 22:17, Soren Wacker wrote:
> Hi,
>
> is it possible with RDKit to generate all stereoisomers of a given 
> compound?
>
> If not, is anyone working on it?
>
> If not, how difficult would it be / what would be the best way to 
> implement such a function.
>
> best regards
>
> Soren
>
>
> ------------------------------------------------------------------------------
>
>
> _______________________________________________
> Rdkit-discuss mailing list
> Rdk...@li...
> https://lists.sourceforge.net/lists/listinfo/rdkit-discuss

Re: [Rdkit-discuss] Generation of stereo-isomers

[Axel P. <axe...@gm...>]

Hi Soren,

maybe this function which enumerates racemates with one stereocenter 
into the corresponding enantiomers might help:

def enum_racemates(sdf_list_or_file, find_only=True, mol_id="molid"):
     """returns: result_sdf::list<mol>, racemic_molids::list<int>
     find_only==True:  return new sdf as list which contains all the 
racemates of the input sdf.
     find_only==False: return new sdf as list with ALL input structures, 
where the racemates are
                       replaced by their two enantiomers. The returned 
sdf is always
                       equal in size or larger as the input sdf.
     Multiple stereo centers are not yet handled.
     In the new sdf the molids are no longer unique and should be reassigned
     (remove molid and run calc_props(sdf))."""

     result_sdf = Mol_List()
     racemic_molids = []

     if not isinstance(sdf_list_or_file, list) and 
sdf_list_or_file.atEnd(): # sdf is file
         print("  * file object is at end, please reload.")
         return None

     for mol in sdf_list_or_file:
         first_undefined = False
         chiral_centers  = Chem.FindMolChiralCenters(mol, 
includeUnassigned=True)

         if chiral_centers:
             first_center    = chiral_centers[0][0]
             first_undefined = chiral_centers[0][1] == "?"

         if first_undefined:
             racemic_molids.append(int(mol.GetProp(mol_id)))
             if find_only:
                 result_sdf.append(mol)
                 continue

             else:
                 mol1 = Chem.Mol(mol)
                 mol2 = Chem.Mol(mol)
mol1.GetAtomWithIdx(first_center).SetChiralTag(Chem.rdchem.ChiralType.CHI_TETRAHEDRAL_CW)
mol2.GetAtomWithIdx(first_center).SetChiralTag(Chem.rdchem.ChiralType.CHI_TETRAHEDRAL_CCW)
                 result_sdf.append(mol1)
                 result_sdf.append(mol2)

         else:
             if not find_only: # return ALL mols
                 result_sdf.append(mol)

     return result_sdf, racemic_molids

Please also have a look at this post 
http://sourceforge.net/p/rdkit/mailman/message/32390126/ and Toby's 
answer which pointed me in the right direction.

Kind regards,
Axel

On 24.09.2015 23:17, Soren Wacker wrote:
> Hi,
>
> is it possible with RDKit to generate all stereoisomers of a given 
> compound?
>
> If not, is anyone working on it?
>
> If not, how difficult would it be / what would be the best way to 
> implement such a function.
>
> best regards
>
> Soren
>
>
> ------------------------------------------------------------------------------
>
>
> _______________________________________________
> Rdkit-discuss mailing list
> Rdk...@li...
> https://lists.sourceforge.net/lists/listinfo/rdkit-discuss

Re: [Rdkit-discuss] Generation of stereo-isomers

[Soren W. <soe...@gm...>]

Hi all,

I opened an issue at rdkit-github for that matter.

https://github.com/rdkit/rdkit/issues/626

Thanks to your comments! If you want look at the code snippet I posted.
At the moment, simply all stereo-isomers are generated.

regards
Soren

On Fri, Sep 25, 2015 at 12:19 AM, Axel Pahl <axe...@gm...> wrote:

> Hi Soren,
>
> maybe this function which enumerates racemates with one stereocenter into
> the corresponding enantiomers might help:
>
> def enum_racemates(sdf_list_or_file, find_only=True, mol_id="molid"):
>     """returns: result_sdf::list<mol>, racemic_molids::list<int>
>     find_only==True:  return new sdf as list which contains all the
> racemates of the input sdf.
>     find_only==False: return new sdf as list with ALL input structures,
> where the racemates are
>                       replaced by their two enantiomers. The returned sdf
> is always
>                       equal in size or larger as the input sdf.
>     Multiple stereo centers are not yet handled.
>     In the new sdf the molids are no longer unique and should be reassigned
>     (remove molid and run calc_props(sdf))."""
>
>     result_sdf = Mol_List()
>     racemic_molids = []
>
>     if not isinstance(sdf_list_or_file, list) and
> sdf_list_or_file.atEnd(): # sdf is file
>         print("  * file object is at end, please reload.")
>         return None
>
>     for mol in sdf_list_or_file:
>         first_undefined = False
>         chiral_centers  = Chem.FindMolChiralCenters(mol,
> includeUnassigned=True)
>
>         if chiral_centers:
>             first_center    = chiral_centers[0][0]
>             first_undefined = chiral_centers[0][1] == "?"
>
>         if first_undefined:
>             racemic_molids.append(int(mol.GetProp(mol_id)))
>             if find_only:
>                 result_sdf.append(mol)
>                 continue
>
>             else:
>                 mol1 = Chem.Mol(mol)
>                 mol2 = Chem.Mol(mol)
>
> mol1.GetAtomWithIdx(first_center).SetChiralTag(Chem.rdchem.ChiralType.CHI_TETRAHEDRAL_CW)
>
> mol2.GetAtomWithIdx(first_center).SetChiralTag(Chem.rdchem.ChiralType.CHI_TETRAHEDRAL_CCW)
>                 result_sdf.append(mol1)
>                 result_sdf.append(mol2)
>
>         else:
>             if not find_only: # return ALL mols
>                 result_sdf.append(mol)
>
>     return result_sdf, racemic_molids
>
> Please also have a look at this post
> http://sourceforge.net/p/rdkit/mailman/message/32390126/ and Toby's
> answer which pointed me in the right direction.
>
> Kind regards,
> Axel
>
>
> On 24.09.2015 23:17, Soren Wacker wrote:
>
> Hi,
>
> is it possible with RDKit to generate all stereoisomers of a given
> compound?
>
> If not, is anyone working on it?
>
> If not, how difficult would it be / what would be the best way to
> implement such a function.
>
> best regards
>
> Soren
>
>
> ------------------------------------------------------------------------------
>
>
>
> _______________________________________________
> Rdkit-discuss mailing lis...@li...://lists.sourceforge.net/lists/listinfo/rdkit-discuss
>
>
>
>
> ------------------------------------------------------------------------------
>
> _______________________________________________
> Rdkit-discuss mailing list
> Rdk...@li...
> https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
>
>