I don't know the exact glide procedure, but I did write such a system for
OpenEye (POSIT). The issue you are facing is that the RMSD portion is just
a constraint used for docking, it isn't used as the "score", in fact, it
can't tell if the conformation interpenetrates the active site or which
orientation is better.
I believe RDKit can generate conformations with a template, see
AllChem.ConstrainedEmbed, this would solve half of your problem in creating
conformations that match your template. You still have the problem with
scoring against your active site. POSIT scored against the shape tanimoto
of the active ligands (if any) to try to fill the same space as the known
ligands. See rdkit.Chem.rdShapeHelpers.ShapeTanimotoDist
This might not be what you want, but we had good success with similar
methods and virtual screening, especially when using multiple co-crystal
active sites. I can send you a reference link if this interests you
Cheers,
Brian
On Mon, Feb 20, 2017 at 12:17 PM, Thomas Evangelidis <teva...@gmail.com>
wrote:
>
> Greg and Brian,
>
> Thank you for your useful hints. All the compounds that I want to align
> are supposed to belong to the same analogue series so they should shave a
> common substructure with substantial size.
>
> What I want to emulate is the "core restrained docking" with glide, where
> you specify the common core of the query and the reference ligand using a
> SMARTS pattern and then glide docks the query compound to the binding
> pocket but takes care to overlay the core atoms of the query to the core
> atoms of the reference compound. Since RDKit does not do docking, I just
> generate 30 conformers of each query compound and select the best one by
> measuring the RMSD between the core of the query and the core of the
> reference after the alignment. Of course the conformations of the core
> atoms between the query and the reference are never identical hence the bad
> alignment. Is there any smarter way to emulate the "core restrained
> docking" with RDKit?
>
> I will provide you with more info soon (example sdf, results, etc.).
>
>
>
>
>
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