Re: [Rdkit-discuss] HasSubstructMatch doesn't work as expected

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

On Thu, Sep 14, 2017 at 12:05 PM, Michał Nowotka <mm...@gm...> wrote:

> Using
>
>     params = AdjustQueryParameters()
>     params.makeAtomsGeneric = True
>     params.makeBondsGeneric = True
>     pattern = AdjustQueryProperties(pattern, params)
>
> Seems to solve my problem - I'm getting a match now (but I haven't yet
> verified if the match is correct and I don't understand why I had to
> set both flags, I'd expect that setting makeBondsGeneric should make
> it work already).
>

I don't think you should need to do "makeAtomsGeneric", but you likely want
to do params.adjustDegree=False.

it's worth being careful with makeBondsGeneric... there you could match
single against triple, which is unlikely to be you want.



> Thank you, Greg!
>
> On Thu, Sep 14, 2017 at 5:58 AM, Greg Landrum <gre...@gm...>
> wrote:
> > This isn't a really straightforward one.
> >
> > One solution (and I think the best one) is to change the aromaticity
> model
> > used to match whatever is generating the hits (in your case it's the
> Symyx
> > cartridge).
> > The RDKit has functionality to do this already when you call the
> > SetAromaticity() function:
> >
> > In [29]: m2 = Chem.MolFromMolFile('./CHEMBL25.mol',sanitize=False)
> >
> > In [30]: Chem.SanitizeMol(m2,Chem.SANITIZE_ALL^Chem.SANITIZE_
> SETAROMATICITY)
> > Out[30]: rdkit.Chem.rdmolops.SanitizeFlags.SANITIZE_NONE
> >
> > In [31]: Chem.SetAromaticity(m2,Chem.AROMATICITY_SIMPLE)
> >
> >
> > The problem here is that there isn't an aromaticity model there for
> > MDL/Symyx. This would be a useful thing to have and can be done quickly.
> If
> > someone can describe the aromaticity model to me, or point me to a
> > description of it, I can add it for the next release (which happens
> soon).
> >
> > Another solution that I think would work is to read the query molecule in
> > without doing aromaticity perception (see input line 30 above) and then
> to
> > convert all the bonds to either single-or-aromatic or double-or-aromatic
> > queries using the approaches described here:
> > http://rdkit.blogspot.ch/2015/08/tuning-substructure-queries.html
> > and here:
> > http://rdkit.blogspot.ch/2016/07/tuning-substructure-queries-ii.html
> >
> > Unfortunately the AdjustQueryParameters function doesn't have anything
> that
> > helps with the kind of bond queries you need, so you'd need to make the
> bond
> > changes in your code. If you want to go down this road and it's not clear
> > how to do so, let me know and I can post some sample code. I'm afraid
> it's
> > not completely trivial with bond queries
> >
> > -greg
> >
> >
> >
> > On Wed, Sep 13, 2017 at 4:42 PM, Michał Nowotka <mm...@gm...>
> wrote:
> >>
> >> Is there any flag in RDkit to match both 'normal' aspirin and embedded
> >> aromatic analogues?
> >> The problem is that I can't modify user queries by hand in real time :)
> >>
> >> On Wed, Sep 13, 2017 at 2:12 PM, Chris Earnshaw <cge...@gm...>
> >> wrote:
> >> > Hi
> >> >
> >> > The problem is due to RDkit perceiving the embedded pyranone in
> >> > CHEMBL1999443 as an aromatic system, which is probably correct.
> However,
> >> > in
> >> > the structure of aspirin the carboxyl carbon and singly bonded oxygen
> >> > are
> >> > non-aromatic, so if you just use the SMILES of aspirin as a query it
> >> > won't
> >> > match CHEMBL1999443
> >> >
> >> > You'll need to use a slightly more generic aspirin-like query to allow
> >> > the
> >> > possibility of matching both 'normal' aspirin and embedded aromatic
> >> > analogues. CC(=O)Oc1ccccc1[#6](=O)[#8] should work OK.
> >> >
> >> > Regards,
> >> > Chris
> >> >
> >> > On 13 September 2017 at 13:40, Michał Nowotka <mm...@gm...>
> wrote:
> >> >>
> >> >> Hi,
> >> >>
> >> >> This problem is probably due to my lack of chemistry knowledge but
> >> >> plese have a look:
> >> >>
> >> >> If I do a substructure search in ChEMBL using aspirin (CHEMBL25) as a
> >> >> query (ChEMBL API uses the Symix catridge):
> >> >>
> >> >>     from chembl_webresource_client.new_client import new_client
> >> >>     res = new_client.substructure.filter(chembl_id='CHEMBL25')
> >> >>
> >> >> One of them will be CHEMBL1999443:
> >> >>
> >> >>     'CHEMBL1999443' in (r['molecule_chembl_id'] for r in res)
> >> >>     >>> True
> >> >>
> >> >> Now I take the molfile:
> >> >>
> >> >>     new_client.molecule.set_format('mol')
> >> >>     mol = new_client.molecule.get('CHEMBL1999443')
> >> >>
> >> >> and load it with aspirin into rdkit:
> >> >>
> >> >>     from rdkit import Chem
> >> >>     m = Chem.MolFromMolBlock(mol)
> >> >>     pattern = Chem.MolFromMolBlock(new_
> client.molecule.get('CHEMBL25'))
> >> >>
> >> >> If I check if it has an aspirin as a substructure using rdkit, I'm
> >> >> getting false...
> >> >>
> >> >>     m.HasSubstructMatch(pattern)
> >> >>     >>> False
> >> >>
> >> >> Looking at this blog post:
> >> >>
> >> >>
> >> >> https://github.com/rdkit/rdkit-tutorials/blob/master/
> notebooks/002_SMARTS_SubstructureMatching.ipynb
> >> >> I tried to initialize rings and retry:
> >> >>
> >> >>      Chem.GetSymmSSSR(m)
> >> >>      m.HasSubstructMatch(pattern)
> >> >>      >>>False
> >> >>
> >> >>     Chem.GetSymmSSSR(pattern)
> >> >>     m.HasSubstructMatch(pattern)
> >> >>     >>>False
> >> >>
> >> >> But as you can see without any luck. Is there anything else I can do
> >> >> to get the match anyway?
> >> >> Without having a match I can't aligh and higlight asprin substructure
> >> >> in CHEMBL1999443 image using GenerateDepictionMatching2DStructure
> and
> >> >> DrawMolecule functions.
> >> >>
> >> >> Kind regards,
> >> >>
> >> >> Michał Nowotka
> >> >>
> >> >>
> >> >>
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> >> >
> >> >
> >>
> >>
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