Re: [Rdkit-discuss] tautomers in rdkit

[Peter S. Shenkin]

 list at
>>> rdkit-discuss-ow...@lists.sourceforge.net
>>>
>>> When replying, please edit your Subject line so it is more specific
>>> than "Re: Contents of Rdkit-discuss digest..."
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>>>
>>> Today's Topics:
>>>
>>>1. tautomers in rdkit (MARIA BRANDL)
>>>2. Re: tautomers in rdkit (Peter S. Shenkin)
>>>3. official Tripos MOL2 file format PDF document (Francois BERENGER)
>>>
>>>
>>> --
>>>
>>> Message: 1
>>> Date: Tue, 11 Apr 2017 06:43:39 + (UTC)
>>> From: MARIA BRANDL 
>>> Subject: [Rdkit-discuss] tautomers in rdkit
>>> To: "rdkit-discuss@lists.sourceforge.net"
>>> 
>>> Message-ID: <1522420730.263132.1491893019...@mail.yahoo.com>
>>> Content-Type: text/plain; charset="utf-8"
>>>
>>> Dear all,
>>>
>>> Is there going to be an attempt at coding Roger Sayle's ?"Alternative
>>> Approach" to tautomers described inRDKit: Six Not-So-Easy Pieces [RDKit UGM
>>> 2016]?into RDKit ?
>>>
>>>
>>> I have managed to get reasonable tautomers out of Resonance.cpp using:
>>> suppl = 
>>> rdchem.ResonanceMolSupplier(m,rdchem.ResonanceFlags.ALLOW_CHARGE_SEPARATION
>>> | \? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? 
>>> rdchem.ResonanceFlags.ALLOW_INCOMPLETE_OCTETS
>>> | \? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? 
>>> rdchem.ResonanceFlags.UNCONSTRAINED_CATIONS
>>> | \? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? rdchem.ResonanceFlags.UNCONSTR
>>> AINED_ANIONS)
>>> ?with some post-filtering for e.g. carbocations, but feel that it may be
>>> more efficient to put user defined constraints on each atom during the
>>> backtracking loops, as Roger suggests.
>>> Looking forward to hearing your thoughts on this.
>>> Best regards,
>>> Maria Brandl
>>> -- next part --
>>> An HTML attachment was scrubbed...
>>>
>>> --
>>>
>>> Message: 2
>>> Date: Tue, 11 Apr 2017 03:47:47 -0400
>>> From: "Peter S. Shenkin" 
>>> Subject: Re: [Rdkit-discuss] tautomers in rdkit
>>> To: MARIA BRANDL 
>>> Cc: "rdkit-discuss@lists.sourceforge.net"
>>> 
>>> Message-ID:
>>> >> ail.com>
>>> Content-Type: text/plain; charset="utf-8"
>>>
>>> Just from the slides, it's not clear that Roger had a solution; the
>>> slides
>>> seem to just suggest an approach. Am I missing something here?
>>>
>>> That is, he defined the invariants that all tautomers of a compound have
>>> to
>>> share and expressed it as a SMARTS + constraints; but I didn't see that
>>> he
>>> provided a methodology to derive a canonical matching SMILES from a
>>> SMARTS
>>> + constraints. True, if two structures match the SMARTS + constraints,
>>> they
>>> are likely tautomers. (I can't think of why they wouldn't be, but maybe
>>> it's not always the case.) So that part provides deduplication of an
>>> input
>>> stream, which is good, but no way to derive and store a canonical
>>> representation.
>>>
>>> Again, perhaps I'm missing something, but if so, what?
>>>
>>> -P.
>>>
>>> On Tue, Apr 11, 2017 at 2:43 AM, MARIA BRANDL 
>>> wrote:
>>>
>>> > Dear all,
>>> >
>>> >
>>> > Is there going to be an attempt at coding Roger Sayle's  "Alternative
>>> > Approach" to tautomers described in
>>> > RDKit: Six Not-So-Easy Pieces [RDKit UGM 2016]
>>> > <https://de.slideshare.net/NextMoveSoftware/rdkit-six-notsoe
>>> asy-pieces-rdkit-ugm-2016> into
>>> > RDKit ?
>>> >
>>> >
>>> > I have managed to get reasonable tautomers out of Resonance.cpp using:
>>> >
>>> > suppl = rdchem.ResonanceMolSupplier(m,rdchem.ResonanceFlags.ALLOW_CH
>>> ARGE_SEPARATION
>>> > | \
>>> >   rdchem.ResonanceFlags.ALLOW_I
>>> NCOMPLETE_OCTETS
>>> > | \
>>> >   rdchem.ResonanceFlags.UNCONST
>>> RAINED_CATIONS
>>> > | \
>>> >   

Re: [Rdkit-discuss] tautomers in rdkit

[David Cosgrove]

Hi JW et al.,
One of the last things I worked on before leaving AZ was what we called a
tautomer-independent molecular representation. What we meant by this was a
way of spotting whether a new compound being registered into the corporate
collectin was a tautomer of one already in the database.  As part of that,
I looked at the InChi representation and the tautomer handling which was at
that point labelled experimental.  In our view, it was very limited in the
types of tautomers it represented and not adequate to our needs.  As a
result I developed a program called tt_tauts, which AZ "open-sourced" when
they made me redundant, and is available at
https://github.com/OpenEye-Contrib/TT_Tauts.  It's another plug for OEChem,
I'm afraid, which seems poor form on the RDKit website, but there you go.
It is also a long way from being complete, and I am still working on it as
a somewhat masochistic hobby.  Internally at CozChemIx Towers it is known
as 'The Mole Project' in honour of the game 'Whac-A-Mole' (
https://en.wikipedia.org/wiki/Whac-A-Mole) - every time you squash an odd
tautomer case, another one pops up, quite often one you've already dealt
with.  Chembl is a marvelous source of nasty test cases.  I hope to have a
better version on github soon and also a description of the algorithm on my
website.  It used as a jumping off point the work of Thalheim et al. (
http://onlinelibrary.wiley.com/doi/10.1002/minf.201400128/full).
Note that this use of tautomer enumeration/representation is somewhat
different from that of quacpac or taut_enum. These last two are concerned
with predicting tautomers likely to be present in water (well, blood,
probably) at roughly neutral pH, the first is trying to deal with two
chemists drawing the same compound in different tautomers which may look
quite different, with the hydrogen atoms shifted a long way. Both are
difficult and unsolved problems.  In one of Roger Sayle's papers on
tautomers, IIRC, he gives an example of a large chemical supplier who
offered two tautomers of the same compound for sale at very different
prices which is at least embarrassing.
Cheers,
Dave

On Tue, Apr 18, 2017 at 1:23 AM, JW Feng  wrote:

> Hi Maria,
>
> From looking at Roger's slides on https://github.com/rdkit/UGM_2
> 016/blob/master/Presentations/Sayle_RDKitTautomers.pdf.  Is he making an
> argument that InChi values are insufficient in generating a canonical
> string for different tautomers?  What if you perform a set of
> standardization transformation prior to generating InChi values?  You may
> want to look at how Genentech normalizes molecules for compound
> registration. The code is based on OEChem and is open sourced on Github
> https://github.com/chemalot/chemalot.  This package is actively being
> developed and I am a contributor.  Specifically, you'll want to look at the
> extensive standardization transformations in
> https://github.com/chemalot/chemalot/blob/master/src/com/gen
> entech/struchk/oeStruchk/Struchk.xml
>
> The last step in Struchk.xml is creating a canonical tautomer using
> OpenEye's QuacPac toolkit.  QuacPac returns a canonical tautomer.  Could
> one replace this step by converting a standardized molecule to InChi and
> the back?  Another approach is using Dave Cosgrove's TautEnum package (
> https://github.com/OpenEye-Contrib/TautEnum).  Both QuacPac and TautEnum
> enumerates tautomers.  I believe that Roger is intimately familiar with
> QuacPac
>
> Best,
>
> JW
>
> ___
> JW Feng, Ph.D.
> Denali Therapeutics Inc.
> 151 Oyster Point Blvd, 2nd Floor, South San Francisco, CA 94080 | (650)
> 270-0628
>
> On Tue, Apr 11, 2017 at 6:52 AM,  ourceforge.net> wrote:
>
>> Send Rdkit-discuss mailing list submissions to
>> rdkit-discuss@lists.sourceforge.net
>>
>> To subscribe or unsubscribe via the World Wide Web, visit
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>>
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>> rdkit-discuss-ow...@lists.sourceforge.net
>>
>> When replying, please edit your Subject line so it is more specific
>> than "Re: Contents of Rdkit-discuss digest..."
>>
>>
>> Today's Topics:
>>
>>1. tautomers in rdkit (MARIA BRANDL)
>>    2. Re: tautomers in rdkit (Peter S. Shenkin)
>>3. official Tripos MOL2 file format PDF document (Francois BERENGER)
>>
>>
>> --
>>
>> Message: 1
>> Date: Tue, 11 Apr 2017 06:43:39 + (UTC)
>> From: MARIA BRANDL 
>>

Re: [Rdkit-discuss] tautomers in rdkit

[JW Feng]

Hi Maria,

>From looking at Roger's slides on https://github.com/rdkit/UGM_2
016/blob/master/Presentations/Sayle_RDKitTautomers.pdf.  Is he making an
argument that InChi values are insufficient in generating a canonical
string for different tautomers?  What if you perform a set of
standardization transformation prior to generating InChi values?  You may
want to look at how Genentech normalizes molecules for compound
registration. The code is based on OEChem and is open sourced on Github
https://github.com/chemalot/chemalot.  This package is actively being
developed and I am a contributor.  Specifically, you'll want to look at the
extensive standardization transformations in https://github.com/chemalot/ch
emalot/blob/master/src/com/genentech/struchk/oeStruchk/Struchk.xml

The last step in Struchk.xml is creating a canonical tautomer using
OpenEye's QuacPac toolkit.  QuacPac returns a canonical tautomer.  Could
one replace this step by converting a standardized molecule to InChi and
the back?  Another approach is using Dave Cosgrove's TautEnum package (
https://github.com/OpenEye-Contrib/TautEnum).  Both QuacPac and TautEnum
enumerates tautomers.  I believe that Roger is intimately familiar with
QuacPac

Best,

JW

___
JW Feng, Ph.D.
Denali Therapeutics Inc.
151 Oyster Point Blvd, 2nd Floor, South San Francisco, CA 94080 | (650)
270-0628

On Tue, Apr 11, 2017 at 6:52 AM,  wrote:

> Send Rdkit-discuss mailing list submissions to
> rdkit-discuss@lists.sourceforge.net
>
> To subscribe or unsubscribe via the World Wide Web, visit
> https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
> or, via email, send a message with subject or body 'help' to
> rdkit-discuss-requ...@lists.sourceforge.net
>
> You can reach the person managing the list at
> rdkit-discuss-ow...@lists.sourceforge.net
>
> When replying, please edit your Subject line so it is more specific
> than "Re: Contents of Rdkit-discuss digest..."
>
>
> Today's Topics:
>
>1. tautomers in rdkit (MARIA BRANDL)
>2. Re: tautomers in rdkit (Peter S. Shenkin)
>3. official Tripos MOL2 file format PDF document (Francois BERENGER)
>
>
> ----------
>
> Message: 1
> Date: Tue, 11 Apr 2017 06:43:39 + (UTC)
> From: MARIA BRANDL 
> Subject: [Rdkit-discuss] tautomers in rdkit
> To: "rdkit-discuss@lists.sourceforge.net"
> 
> Message-ID: <1522420730.263132.1491893019...@mail.yahoo.com>
> Content-Type: text/plain; charset="utf-8"
>
> Dear all,
>
> Is there going to be an attempt at coding Roger Sayle's ?"Alternative
> Approach" to tautomers described inRDKit: Six Not-So-Easy Pieces [RDKit UGM
> 2016]?into RDKit ?
>
>
> I have managed to get reasonable tautomers out of Resonance.cpp using:
> suppl = 
> rdchem.ResonanceMolSupplier(m,rdchem.ResonanceFlags.ALLOW_CHARGE_SEPARATION
> | \? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? 
> rdchem.ResonanceFlags.ALLOW_INCOMPLETE_OCTETS
> | \? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? 
> rdchem.ResonanceFlags.UNCONSTRAINED_CATIONS
> | \? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? rdchem.ResonanceFlags.UNCONSTR
> AINED_ANIONS)
> ?with some post-filtering for e.g. carbocations, but feel that it may be
> more efficient to put user defined constraints on each atom during the
> backtracking loops, as Roger suggests.
> Looking forward to hearing your thoughts on this.
> Best regards,
> Maria Brandl
> -- next part --
> An HTML attachment was scrubbed...
>
> --
>
> Message: 2
> Date: Tue, 11 Apr 2017 03:47:47 -0400
> From: "Peter S. Shenkin" 
> Subject: Re: [Rdkit-discuss] tautomers in rdkit
> To: MARIA BRANDL 
> Cc: "rdkit-discuss@lists.sourceforge.net"
> 
> Message-ID:
>  ail.com>
> Content-Type: text/plain; charset="utf-8"
>
> Just from the slides, it's not clear that Roger had a solution; the slides
> seem to just suggest an approach. Am I missing something here?
>
> That is, he defined the invariants that all tautomers of a compound have to
> share and expressed it as a SMARTS + constraints; but I didn't see that he
> provided a methodology to derive a canonical matching SMILES from a SMARTS
> + constraints. True, if two structures match the SMARTS + constraints, they
> are likely tautomers. (I can't think of why they wouldn't be, but maybe
> it's not always the case.) So that part provides deduplication of an input
> stream, which is good, but no way to derive and store a canonical
> representation.
>
> Again, perhaps I'm missing something, but if 

Re: [Rdkit-discuss] tautomers in rdkit

[Peter S. Shenkin]

Just from the slides, it's not clear that Roger had a solution; the slides
seem to just suggest an approach. Am I missing something here?

That is, he defined the invariants that all tautomers of a compound have to
share and expressed it as a SMARTS + constraints; but I didn't see that he
provided a methodology to derive a canonical matching SMILES from a SMARTS
+ constraints. True, if two structures match the SMARTS + constraints, they
are likely tautomers. (I can't think of why they wouldn't be, but maybe
it's not always the case.) So that part provides deduplication of an input
stream, which is good, but no way to derive and store a canonical
representation.

Again, perhaps I'm missing something, but if so, what?

-P.

On Tue, Apr 11, 2017 at 2:43 AM, MARIA BRANDL 
wrote:

> Dear all,
>
>
> Is there going to be an attempt at coding Roger Sayle's  "Alternative
> Approach" to tautomers described in
> RDKit: Six Not-So-Easy Pieces [RDKit UGM 2016]
> 
>  into
> RDKit ?
>
>
> I have managed to get reasonable tautomers out of Resonance.cpp using:
>
> suppl = 
> rdchem.ResonanceMolSupplier(m,rdchem.ResonanceFlags.ALLOW_CHARGE_SEPARATION
> | \
>   
> rdchem.ResonanceFlags.ALLOW_INCOMPLETE_OCTETS
> | \
>   
> rdchem.ResonanceFlags.UNCONSTRAINED_CATIONS
> | \
>   rdchem.ResonanceFlags.
> UNCONSTRAINED_ANIONS)
>
>  with some post-filtering for e.g. carbocations, but feel that it may be
> more efficient to put user defined constraints on each atom during the
> backtracking loops, as Roger suggests.
>
> Looking forward to hearing your thoughts on this.
>
> Best regards,
>
> Maria Brandl
>
> 
> --
> Check out the vibrant tech community on one of the world's most
> engaging tech sites, Slashdot.org! http://sdm.link/slashdot
> ___
> Rdkit-discuss mailing list
> Rdkit-discuss@lists.sourceforge.net
> https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
>
>
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[Rdkit-discuss] tautomers in rdkit

[MARIA BRANDL]

Dear all,

Is there going to be an attempt at coding Roger Sayle's  "Alternative Approach" 
to tautomers described inRDKit: Six Not-So-Easy Pieces [RDKit UGM 2016] into 
RDKit ?


I have managed to get reasonable tautomers out of Resonance.cpp using:
suppl = 
rdchem.ResonanceMolSupplier(m,rdchem.ResonanceFlags.ALLOW_CHARGE_SEPARATION | \ 
                                         
rdchem.ResonanceFlags.ALLOW_INCOMPLETE_OCTETS | \                               
           rdchem.ResonanceFlags.UNCONSTRAINED_CATIONS | \                      
                    rdchem.ResonanceFlags.UNCONSTRAINED_ANIONS)
 with some post-filtering for e.g. carbocations, but feel that it may be more 
efficient to put user defined constraints on each atom during the backtracking 
loops, as Roger suggests.
Looking forward to hearing your thoughts on this.
Best regards,
Maria Brandl--
Check out the vibrant tech community on one of the world's most
engaging tech sites, Slashdot.org! http://sdm.link/slashdot___
Rdkit-discuss mailing list
Rdkit-discuss@lists.sourceforge.net
https://lists.sourceforge.net/lists/listinfo/rdkit-discuss