3D generation of both enantiomers from an sd file.

 

I have been using the ChemAxon molconvert tool to take approx 3000 2D structures from an SD file and generate a mol2 file of 3D conformers for docking purposes.  An issue I have run into is that the majority of these compounds have multiple chiral centers.  About 1600 of these compounds are racemates, and so for the purpose of docking I would like to generate two 3D structures per compound - one representing each enantiomer.  I can do this one by one using MarvinSketch, MarvinView, or InstantJChem via the flip/mirror tool, but I would like to do it in batch for all 1600 compounds.

I have searched the forums and come up with a few ideas for how to do this, but I have been unsuccessful in implementing them so far.

I am wondering if I can somehow create a reaction in Reactor that would take the generic molecule and simply flip/mirror it.  I have tried to do a reaction where with a generic chiral carbon (4 R groups attached) undergoes stereochemical inversion, but this results in the generation of all possible diastereomers of compounds with multiple chiral centers, rather than just the enantiomers I am looking for.

Alternatively, is it possible to somehow use molconvert to multiply every coordinate in the mol2 file by -1?  I saw this mentioned in a thread discussing the Java API, but I unfortunately do not know Java and am limited to ChemAxon's command-line and GUI tools.

Thanks in advance for any ideas or assistance with this.

You could try the stereoisomers calculation plugin. It can be used on command-line:

cxcalc -o <outfile1> <infile> stereoisomers -v -3

molconvert mol2 <outfile1> -o <mol2-outfile>

It will calculate the sterosisomers and output them in 3D form to a file. The resulting file can be then simply converted to mol2.

You can find the related documentations here:

http://www.chemaxon.com/marvin/help/applications/calc.html

http://www.chemaxon.com/marvin/help/calculations/isomers.html#stereoisomer

Thanks dzatonyi - the problem with doing the stereoisomers calculation is that it gives me all possible diastereomers for compounds with multiple chiral centers.  For example, when I ran the command you posted above on the 1600 compound SD file, it generated over 5600 compounds.  More than 2000 of these are compounds that do not exist.

If there is not currently a way to easily generate only enantiomers as opposed to all possible diastereomers, could this be considered for future implementation one of the GUI software packages such as Reactor or Standardizer?

I can see the problem.

Actually, there is an API method for enantiomer generation: http://www.chemaxon.com/marvin/help/developer/beans/api/chemaxon/calculations/stereo/Stereochemistry.html#getEnantiomer(T)

So the problem could be solved this way:

MolImporter mi = new MolImporter(<INPUTFILE>);


MolExporter me = new MolExporter(<OUTFILE>, "mol2");


Molecule m = null;


while((m = mi.read()) != null) {


        Molecule mol = Stereochemistry.getEnantiomer(m);


        Cleaner.clean(mol, 3, null);


        me.write(mol);


}


mi.close();


me.close();

A proper enantiomer generator will be considered.

Dzatonyi - Thanks again for the help and for the consideration of this feature in future releases.

In case anyone else has a similar problem, I ended up using this protocol to generate the enantiomers:

1) Used Instant JChem to sort the racemates into bins based on number of chiral carbons

2)  For the compounds with only one chiral carbon, I used the stereoisomers calculator plugin as outlined above, which generated two enantiomers for each compound.

3) For the compounds with multiple chiral carbons, I generated separate SD files for each chiral carbon count (two CCs, three CCs, four CCs etc).  Thankfully these sets were all <200 compounds, so I was able to open each of them in Chemdraw and then generate the enatiomers by Select All -> Flip horizontal and then saving as a new SD file.  This would not be possible for much larger sets, but it was fine in this instance.

4) I then used Instant Jchem to merge the calculator output with  the original multi-chiral center sdfiles and their flipped versions into one large file that I then used to generate the 3D lowest-energy conformers using molconvert.