Re: [Ambit-users] [URGENT] Different results when applying transformations on the same molecule in Kekule and in aromatic forms.

[Nina J. <jel...@gm...>]

Thanks. One more inquiry - could you run  mvn dependency:tree on your
project with ambit 3.0.0 and tell which  net.idea.modbcum-i version is
required

And possibly check if it is here
http://ambit.uni-plovdiv.bg:8083/nexus/#nexus-search;gav~net.idea~modbcum-i~~~~kw,versionexpand

Regards,
Nina

On 23 April 2015 at 20:42, Yannick .Djoumbou <y.d...@gm...> wrote:

> Hi Nina,
>
> I got some help from John regarding kekulization and how to go around type
> 4 bonds. I attached the class SmirksTest.java. Some included CDK classes
> are not in this code though.
>
> I changed my code from the previous one, and I am adding implicit H
> atoms., converting them to explicit ones, and I kekulize the molecule.
> John suggested setting the flag of each bond to ISAROMATIC when its is set
> to SINGLE_OR_DOUBLE, as well as seeting the flag for the 2 participant
> atoms to ISAROMATIC. this is done before kekulaiation (from the
> Kekulization class).
>
> Now, I get metabolites when the input structure is in aromatic (not
> kekule) form (see MOL1, output_1, and mol1_metabolites). however, when I
> submit the structure in kekule form (MOL2, output_2), I do not get any
> metabolite.
>
> The SMIRKS I used is: [c:1][H:2]>>[c:1][OX2][H:2]    (I also tried
> [c;H1:1]>>[c:1][OX2H1])
>
> Thank you for your help.
>
> Regards,
>
>
> On Thu, Apr 23, 2015 at 11:07 AM, Nina Jeliazkova <
> jel...@gm...> wrote:
>
>> Hi Yannick,
>>
>> On 23 April 2015 at 19:17, Yannick .Djoumbou <y.d...@gm...>
>> wrote:
>>
>>> Hi Nina,
>>>
>>> You mentioned early that SMIRKS needs the structures to be kekulized. I
>>> assumed that it means every bond of type 4 will be changed to type 1 or 2,
>>> but still be labeled as aromatic. Am I right?
>>> This means, I should not used the Aromatize function then. I should make
>>> sure the structure is always kekulize. Therefore, I should use the
>>> kekuliseAromaticRings() from FixBondOrdersTool, right?
>>>
>>
>> No, FixBondOrdersTool is deprecated, don't use it.  Use the new
>> Kekulization class. John May may help with how to use it.
>>
>>
>> http://cdk.github.io/cdk/1.5/docs/api/org/openscience/cdk/aromaticity/Kekulization.html
>>
>>
>>>
>>> Moreover, I have the following error when using ambit2 3.0.0. It
>>> tdoesn't mattr whether I use CDK 1.5.6 (as I did before with ambit 2.5.6)
>>> or 1.5.10.
>>>
>>> Exception in thread "main" java.lang.NoClassDefFoundError:
>>> net/idea/modbcum/i/exceptions/AmbitException
>>>     at Metabolize.main(Metabolize.java:35)
>>> Caused by: java.lang.ClassNotFoundException:
>>> net.idea.modbcum.i.exceptions.AmbitException
>>>     at java.net.URLClassLoader$1.run(URLClassLoader.java:366)
>>>     at java.net.URLClassLoader$1.run(URLClassLoader.java:355)
>>>     at java.security.AccessController.doPrivileged(Native Method)
>>>     at java.net.URLClassLoader.findClass(URLClassLoader.java:354)
>>>     at java.lang.ClassLoader.loadClass(ClassLoader.java:424)
>>>     at sun.misc.Launcher$AppClassLoader.loadClass(Launcher.java:308)
>>>     at java.lang.ClassLoader.loadClass(ClassLoader.java:357)
>>>     ... 1 more
>>>
>>> Metabolize.java is the class where I call the main function that uses
>>> the AMBIT and CDK modules. I did not have this error before moving to 3.0.0.
>>>
>>
>> Can you give a piece of code we can test?    It looks like a missing/ not
>> loaded dependency.
>>
>> Regards,
>> Nina
>>
>>
>>
>>> Please let me know.
>>>
>>> Regards,
>>>
>>> On Tue, Apr 21, 2015 at 10:54 PM, Yannick .Djoumbou <
>>> y.d...@gm...> wrote:
>>>
>>>> Thanks for letting me know.
>>>> Regards,
>>>>
>>>> Yannick
>>>>
>>>> On Tue, Apr 21, 2015 at 10:44 PM, Nina Jeliazkova <
>>>> jel...@gm...> wrote:
>>>>
>>>>> Yannick,
>>>>>
>>>>> Just a warning, 3.0.0 is still being tested and not released yet, but
>>>>> the SMIRKS package was tested by another group as well and appears to work
>>>>> well.
>>>>>
>>>>> Best regards,
>>>>> Nina
>>>>>
>>>>>
>>>>> On 22 April 2015 at 07:38, Yannick .Djoumbou <y.d...@gm...>
>>>>> wrote:
>>>>>
>>>>>> Thanks Nina,
>>>>>>
>>>>>> first of all, I am really happy that a new release of AMBIT was
>>>>>> released and is working with CDK 1.5.10. I'll try that out and also use the
>>>>>> aromaticity class.
>>>>>> I a looking forward to reading Nick's reply.
>>>>>>
>>>>>> Regards,
>>>>>>
>>>>>> Yannick
>>>>>>
>>>>>> On Tue, Apr 21, 2015 at 10:32 PM, Nina Jeliazkova <
>>>>>> jel...@gm...> wrote:
>>>>>>
>>>>>>> Yannick,
>>>>>>>
>>>>>>> Nick may reply later this week, but could you please try ambit
>>>>>>> 3.0.0-SNAPSHOT  (CDK 1.5.10) dependency
>>>>>>>
>>>>>>>
>>>>>>> http://ambit.uni-plovdiv.bg:8083/nexus/#nexus-search;gav~ambit~~3.0.0-SNAPSHOT~~
>>>>>>>
>>>>>>> The version you work with is quite outdated and there have been
>>>>>>> number of improvements.
>>>>>>>
>>>>>>> Last but not least, the SMIRKS package expects Kekule structures.
>>>>>>> You will NOT get same results if structures are not kekulized. Fortunately,
>>>>>>> in CDK 1.5.10 the kekulization works quite well.
>>>>>>>
>>>>>>> In any case please do not use SMSD* package, it is already
>>>>>>> deprecated in CDK as far as I know.  Use the new Aromaticity class
>>>>>>>
>>>>>>>
>>>>>>> http://cdk.github.io/cdk/1.5/docs/api/org/openscience/cdk/aromaticity/Aromaticity.html
>>>>>>>
>>>>>>> Best regards,
>>>>>>> Nina
>>>>>>>
>>>>>>>
>>>>>>> On 21 April 2015 at 21:07, Yannick .Djoumbou <y.d...@gm...>
>>>>>>> wrote:
>>>>>>>
>>>>>>>> Hello guys,
>>>>>>>>
>>>>>>>> I am dealing with an issue here. I would like to apply a
>>>>>>>> transformation on the attached molecules. Below is a function that I wrote
>>>>>>>> to apply a transformation with single copy for each position (with
>>>>>>>> smrkMan.applyTransformationWithSingleCopyForEachPos). Because CDK has
>>>>>>>> issues dealing with bond type 4, I tried to transform the same molecule
>>>>>>>> (aniline) using different bond types.
>>>>>>>> In test1.sdf, the bond types in the benzene ring have type 1 and 2,
>>>>>>>> alternatively. This, however produces 5 metabolites. In test2.sdf,
>>>>>>>> the aromatic bonds of the molecule are of type 4. The transformation does
>>>>>>>> not produce any product, which is wrong.
>>>>>>>>
>>>>>>>> Procedure:
>>>>>>>> ----------
>>>>>>>> (1) I tested whether CDK viewed the input molecule as aromatic or
>>>>>>>> not, by checking the bond types. For my own preference, I also
>>>>>>>> added explicit hydrogen atoms in order to use my smirks pattern more
>>>>>>>> efficiently. For test1, aniline is not first viewed as aromatic.
>>>>>>>> Thus, I aromatized it using CDK's SMSDNormalizer.aromatizeMolecule. In
>>>>>>>> test2, aniline is viewed as aromatic. Because the bonds in the benzene ring
>>>>>>>> are of type 4, I decided to kekulize it, so that CDK with better
>>>>>>>> deal with the molecule. Somehow, the resulting molecule still has bond type
>>>>>>>> 4. The resulting molecules after these edits are stored in
>>>>>>>> test1_after_aromatizing_and_adding_hydrogen.sdf and
>>>>>>>> test2_after_kekulizing_and_adding_hydrogen.sdf. Somehow, the molecule in
>>>>>>>> the later files does not have explicit hydrogen atoms attached to the
>>>>>>>> benzene ring.
>>>>>>>>
>>>>>>>> (2) Following the first step, I ran
>>>>>>>> smrkMan.applyTransformationWithSingleCopyForEachPos on the container
>>>>>>>> obtained after the first step, where smrkMan is an instance of the SMRIKS
>>>>>>>> Manager. As mentioned earlier, aniline in the first form (ring bonds with
>>>>>>>> types 1 and 2) was transformed. the five products are in the file
>>>>>>>> test1_metabolites.sdf. In the second file (ring bonds with type 4)
>>>>>>>> is not transformed.
>>>>>>>> I used the smirks: [c;H1:1]>>[c:1][OX2H1] and [c:1]>>[c:1][OX2H1]
>>>>>>>> foe each molecule, which returned the same output.
>>>>>>>>  This procedure was implemented in the function transform_from_sdf
>>>>>>>> below.
>>>>>>>>
>>>>>>>>
>>>>>>>> Could you please help me here? How can I get the same results
>>>>>>>> whether I submit my molecule in the kekule or the aromatic form? I have
>>>>>>>> tried different things, but without success. by the way, I am using the
>>>>>>>> AMBIT 2.6.0 and CDK version 1.5.6 versions. I really need help
>>>>>>>> here.
>>>>>>>>
>>>>>>>> Thank you for your consideration.
>>>>>>>>
>>>>>>>> Best regards,
>>>>>>>>
>>>>>>>> Yannick
>>>>>>>>
>>>>>>>>
>>>>>>>>
>>>>>>>>
>>>>>>>>
>>>>>>>>
>>>>>>>>
>>>>>>>>
>>>>>>>> public LinkedHashMap<String, IAtomContainerSet>
>>>>>>>> transform_from_sdf(File sdf_input, SMIRKSReaction reaction) throws
>>>>>>>> Exception{
>>>>>>>>
>>>>>>>>     LinkedHashMap<String, IAtomContainerSet> sdf_metabolites = new
>>>>>>>> LinkedHashMap<String, IAtomContainerSet>();
>>>>>>>>     IteratingSDFReader reader = new IteratingSDFReader(new
>>>>>>>> FileInputStream(sdf_input), DefaultChemObjectBuilder.getInstance());
>>>>>>>>     SMIRKSManager smrkMan =  new
>>>>>>>> SMIRKSManager(SilentChemObjectBuilder.getInstance());
>>>>>>>>
>>>>>>>>     StringWriter writer=new StringWriter(); //
>>>>>>>> http://www.programcreek.com/java-api-examples/index.php?api=org.openscience.cdk.AtomContainerSet
>>>>>>>>
>>>>>>>>     StructureDiagramGenerator sdg =  new
>>>>>>>> StructureDiagramGenerator();
>>>>>>>>     DeduceBondSystemTool dbst = new DeduceBondSystemTool();
>>>>>>>>     FixBondOrdersTool kekulizer = new FixBondOrdersTool();
>>>>>>>>
>>>>>>>>     int i = 0;
>>>>>>>>     while (reader.hasNext()) {
>>>>>>>>         i = i+1;
>>>>>>>>
>>>>>>>>         IAtomContainer molecule = (IAtomContainer)reader.next();
>>>>>>>>         System.out.println("Query molecule: " + molecule);
>>>>>>>>
>>>>>>>>         boolean aromatic_0 = false;
>>>>>>>>         for (IBond bond : molecule.bonds()) if
>>>>>>>> (bond.getFlag(CDKConstants.ISAROMATIC)) {aromatic_0 = true; break;}
>>>>>>>>
>>>>>>>>         System.out.println("IS THE ORIGINAL MOLECULE AROMATIC?: " +
>>>>>>>> aromatic_0);
>>>>>>>>
>>>>>>>>
>>>>>>>>         StringWriter w = new StringWriter();
>>>>>>>>         MDLWriter mw = new MDLWriter(w);
>>>>>>>>         mw.write(molecule);
>>>>>>>>         System.out.println("ORIGINAL MOLECULE" + w.toString());
>>>>>>>>
>>>>>>>>
>>>>>>>> AtomContainerManipulator.convertImplicitToExplicitHydrogens(molecule);
>>>>>>>>         sdg.setMolecule(molecule);
>>>>>>>>         sdg.generateCoordinates();
>>>>>>>>         IAtomContainer mol_with_hydrogen = sdg.getMolecule();
>>>>>>>>
>>>>>>>>
>>>>>>>>         if(!aromatic_0){
>>>>>>>>             SMSDNormalizer.aromatizeMolecule(mol_with_hydrogen);
>>>>>>>>             boolean aromatic = false;
>>>>>>>>             for (IBond bond : mol_with_hydrogen.bonds()) if
>>>>>>>> (bond.getFlag(CDKConstants.ISAROMATIC)) {aromatic = true; break;}
>>>>>>>>             System.out.println("HAS THE MOLECULE BEEN AROMATIZED?:
>>>>>>>> " + aromatic);
>>>>>>>>             mw.write(mol_with_hydrogen);
>>>>>>>>             System.out.println("AROMATIZED MOLECULE WITH HYDROGEN
>>>>>>>> EXPLICIT ATOMS" + w.toString());
>>>>>>>>
>>>>>>>>         }
>>>>>>>>         else{
>>>>>>>>
>>>>>>>> AtomContainerManipulator.percieveAtomTypesAndConfigureAtoms(mol_with_hydrogen);
>>>>>>>>             mol_with_hydrogen =
>>>>>>>> kekulizer.kekuliseAromaticRings(mol_with_hydrogen);
>>>>>>>>             mw.write(mol_with_hydrogen);
>>>>>>>>             System.out.println(mol_with_hydrogen);
>>>>>>>>             System.out.println("AROMATIZED MOLECULE WITH HYDROGEN
>>>>>>>> EXPLICIT ATOMS" + w.toString());
>>>>>>>>
>>>>>>>>             boolean aromatic_3 = false;
>>>>>>>>             for (IBond bond : mol_with_hydrogen.bonds()) if
>>>>>>>> (bond.getFlag(CDKConstants.ISAROMATIC)) {aromatic_3 = true; break;}
>>>>>>>>             System.out.println("IS AROMATIC AFTER HYDRO?? " +
>>>>>>>> aromatic_3);
>>>>>>>>         }
>>>>>>>>
>>>>>>>>
>>>>>>>>         System.out.println(mol_with_hydrogen);
>>>>>>>>         SmilesGenerator        sg      = new SmilesGenerator();
>>>>>>>>         System.out.println(sg.create(mol_with_hydrogen));
>>>>>>>>
>>>>>>>>
>>>>>>>>         String name = (String)
>>>>>>>> molecule.getProperty(CDKConstants.TITLE);
>>>>>>>>         IAtomContainerSet metabolites =
>>>>>>>> generateAllMetabolitesFromAtomContainer(mol_with_hydrogen, reaction,
>>>>>>>> smrkMan);
>>>>>>>>         System.out.println("METABOLITES" + metabolites);
>>>>>>>> }
>>>>>>>>
>>>>>>>
>>>>>>>
>>>>>>
>>>>>
>>>>
>>>
>>
>