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Re: [Ambit-users] [URGENT] Different results when applying transformations on the same molecule in Kekule and in aromatic forms.
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From: Yannick .D. <y.d...@gm...> - 2015-04-28 18:58:05
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Thanks Nick for the thorough explanation,
My comments below.
I will try to implement it, and then come back to you.
Regards,
Yannick
On Mon, Apr 27, 2015 at 11:20 PM, Nikolay Kochev <ni...@un...>
wrote:
> Hi Yannick
>
> On 4/27/15 7:35 PM, Yannick .Djoumbou wrote:
>
> Hi Nick,
>
> Thanks for the quick reply. I will follow your advice.
> I have followed the example that Nina provided on GitHub, which some
> adjustments. I found that I could not apply transformations targeting atoms
> in an aromatic ring, unless I aromatize the molecule. However, I was told
> that AMBIT works with the kekule form. I ended up trying to aromatize every
> single molecule (not matter whether it was an aromatic or aliphatic one).
> This had the effect that I could apply transformtion both on aliphatic and
> aromatic molecules. This is the only way I found to go around this issue. I
> am not sure though if kekulizing and aromatizing a molecule makes much
> sense.
>
>
> The aromaticity makes a lot of sense because especially for reaction
> transformations.
> When one applies SMIRKS reactions must know in detail what happens to the
> molecule, how it is handle within CDK package.
>
> Technically the SMIRKS transformations can work both for aromatic and
> kekulized structures but working with aromatic structures brings a lot of
> side effects and for each reaction one must chemically reason whether the
> obtained molecule is correct and eventually apply specific CDK based post
> processing of the reaction products.
> The side effects are due to the facts that the reacitons mainly change the
> bond orders and when the molecule is represented as aromatic form some bond
> orders may not be defined explicitly.
>
>
> That is way we recommend following approach:
> (1) Convert structure to Kekule form (aromaticity must be present detected
> before that)
> (2) Apply reaction
> (3) Detect aromaticity again
> (4) Eventually if one interested convert to aromatic form (KEKULE -->
> aromatic)
>
> We have a nice feature in the SMIRKS manager called
> FlagProcessResultStructures. By defaults it is false. I recommend you that
> you set it to true.
> It will configure the resulting molecules and detect aromaticity for the
> product.
> Then if interested step (4) may be done
>
>
>
> For every bond in the molecule, I appy this
>
> for (IBond bond : molecule.bonds()){
> if (bond.getFlag(CDKConstants.SINGLE_OR_DOUBLE)){
> bond.setFlag(CDKConstants.ISAROMATIC, true);
> bond.getAtom(0).setFlag(CDKConstants.ISAROMATIC, true);
> bond.getAtom(1).setFlag(CDKConstants.ISAROMATIC, true);
> }
> }
> Then, I kekulize the molecule. I can apply transformations targeting
> atoms in the aliphatic parts of the molecule only. But when I aromatize, I
> can apply any transformation to the molecule (as long as the targeted
> pattern is present).
>
>
> When reaction is applied it is good that the molecule is in Kekule form
> but it has the aromatic flags set as well. If it is the case, then the
> function processProduct is called, which will clear aromaticity, since
> FlagClearAromaticityBeforeResultProcess is set to true by default. So, how
> would this work?
>
>
> Also bear in mind that:
> [C] is aliphatic cartbon, [c] is aromatic carbon and [#6] is any carbon.
> So this [#7:1][C:2]([H]) would be applied only for aliphatic carbon (or
> if the molecule is not configured well for C atom which do not have
> aromatic flags set)
>
>
> Nick
>
>
> Regards,
>
> Yannick
>
>
>
> On Mon, Apr 27, 2015 at 6:17 AM, Nikolay Kochev <ni...@un...>
> wrote:
>
>> Hello Yannick
>>
>>
>> On 2015-04-27 00:55, Yannick .Djoumbou wrote:
>>
>>> Hello Nina,
>>>
>>> Thanks a lot for the help. This is great stuff. I still have an issue
>>> because, I cannot generate aromatic transformation (e.g.: aromatic
>>> hydroxylation) when the molecule is just kekulized. I have to apply
>>> the aromaticity.apply(molecule) if I am targeting aromatic atoms.
>>> Moreover, in some cases, e.g.: N-dealkylation, one ends up often with
>>> more than one moiety. For example, applying:
>>> - the smirks: [#7:1][C:2]([H])>>[#7:1][H].[C:2]=[O]
>>> - to the molecule "OCCNC1=CC=CC=C1"
>>> - using the function applyTransformationWithSingleCopyForEachPos
>>>
>>> will return the following AtomContainer: C=1(C=CC=CC1)N.C(CO)=O.
>>>
>>>
>> Yes that is exactly the expected result. You have two fragments
>> (molecules) within the result atom container.
>>
>>
>> These are actually two different molecles representing two different
>>> products. Is there a way to change this so that ambit returns each
>>> moiety as an actual molecule?
>>>
>>
>> If you need each molecule as a different IAtomContanier object you can
>> use a code like this
>>
>>
>> IAtomContainerSet ms = ConnectivityChecker.partitionIntoMolecules(mol);
>>
>> where the mol is the result from the reaction.
>>
>> The you iterate ms (container/molecule set)
>>
>>
>> Best regards
>> Nick
>>
>>
>>
>> So far, one could go around by applying
>>
>>> two smirks, each of which has one of the two products smarts:
>>> [#7:1][C:2]([H])>>[#7:1][H]
>>> [#7:1][C:2]([H])>>[C:2]=[O]
>>>
>>>
>>
>>
>>
>> However, if would be awesome if the resulting AtomContainerSet from
>>> applyTransformationWithSingleCopyForEachPos would actually contain
>>> each moiety as a separate AtomContainer.
>>>
>>> Thanks a lot for the great assistance.
>>>
>>> Regards,
>>>
>>> Yannick
>>>
>>> On Sun, Apr 26, 2015 at 1:16 AM, Nina Jeliazkova
>>> <jel...@gm...> wrote:
>>>
>>> Yannick, All,
>>>>
>>>> I've added a small Maven project demonstrating how to use the SMIRKS
>>>> code and configure the dependencies.
>>>>
>>>>
>>>>
>>> https://github.com/ideaconsult/examples-ambit/tree/master/smirks-example
>>>
>>>> [1]
>>>>
>>>> Best regards,
>>>> Nina
>>>>
>>>
>>>
>>>
>>> Links:
>>> ------
>>> [1]
>>> https://github.com/ideaconsult/examples-ambit/tree/master/smirks-example
>>>
>>
>>
>
>
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