Hello Thomas,

This publication could be of interest to you. I have not read the whole
paper so I don't know how relevant it is.

Ling

Graph-Based Molecular Alignment (GMA)
Marialke, Korner, Tietze, Apostolakis
J. Chem. Inf. Model. 47 (2007) 591-601


On Mon, Feb 20, 2017 at 3:32 PM, Thomas Evangelidis <teva...@gmail.com>
wrote:

> @Peter
> I am working exactly on the scenario you described.
>
> @Brian
> I have found this thread which is pretty similar to my case and to what
> you suggested, so now I am adapting my code accordingly.
>
> https://sourceforge.net/p/rdkit/mailman/message/35034093/
>
> What you have published sounds interesting. I also have multiple
> co-crystal active sites. Could you please send me the link?
> One question: what was more successful in your experience when you had a
> crystal ligand and a series of analogues that you wanted to place into the
> binding pocket? 1) to superpose the MCS between the scaffold of the query
> and the crystal ligand, or the MCS of the whole molecules?
>
>
>
>
> On 20 February 2017 at 21:03, Peter S. Shenkin <shen...@gmail.com> wrote:
>
>> With Glide, IIRC, this facility is designed for the use case where the
>> coordinates of a docked ligand are known (typically from an X-ray
>> structure) and the docked ligand shares a SMARTS with the ligands in an
>> input file. The SMARTS-matching atoms of each incoming ligand are
>> superposed upon the corresponding atoms of the docked ligand and the
>> resulting pose is used as an initial guess for the docking.
>>
>> Some notes:
>>
>> 0. Greg questions whether there is really a common core in your example,
>> and if there's not, it doesn't appear as if the procedure is directly
>> applicable. But if it is applicable, read on.
>>
>> 1. If the SMARTS matches in multiple ways, all are tried, and the best
>> docking score among them wins (though there may be a way of requesting the
>> N best scores, or even all of them). So if the SMARTS specifies a phenyl
>> ring, for example, 12 initial poses will be tried. (If it contains two
>> phenyl rings, 24 will be tried....)
>>
>> 2. GLIDE itself does conformer generation, but I'm not sure how it works
>> in this procedure. If the SMARTS specifies a rigid core, you probably don't
>> need to pre-generate conformers, but if the core is flexible, you are
>> probably best off generating them, which of course you are permitted to do.
>>
>> 3. If you have GLIDE, then  you probably have LigPrep as well. The
>> advantage of using LigPrep for your conformation generation would be that
>> the strain energy would be written into the output file, and then, when
>> used as the input to Glide, it would be taken into account when computing
>> the docking score. And it uses the same (or a very similar) force-field
>> that Glide itself uses.
>>
>> 4. I may have some details slightly incorrect, so you might want to
>> address your question to Schrödinger tech support.
>>
>> On Mon, Feb 20, 2017 at 2:15 PM, Brian Kelley <fustiga...@gmail.com>
>> wrote:
>>
>>> 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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>>>
>>
>
>
> --
>
> ======================================================================
>
> Thomas Evangelidis
>
> Research Specialist
> CEITEC - Central European Institute of Technology
> Masaryk University
> Kamenice 5/A35/1S081,
> 62500 Brno, Czech Republic
>
> email: tev...@pharm.uoa.gr
>
>           teva...@gmail.com
>
>
> website: https://sites.google.com/site/thomasevangelidishomepage/
>
>
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