Is there a way to prevent (re)protonation during conformer generation?

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Is there a way to prevent (re)protonation during conformer generation?

mirix
I am generating 3D structures from canonical SMILES and I am facing several issues.

The first is that OpenBabel does not seem to be able to produce structures with the right sterochemistry in certain cases (even if it is explicitly indicated in the SMILES). As far as I can tell, this happens with fused rings where both (contiguous) shared atoms are sterocenters.

The workaround I found is converting the SMILES to mol2 with Balloon (because Omega2 fails with a few of them) and then:

obabel ${ligandid}.mol2 -O ${ligandid}.sdf --conformer --nconf 200 --score energy --writeconformers

The problem is that obabel seems to reprotonate certain functional groups (such as carboxylic acids which are deprotonated on purpose). Is there a way to prevent such behaviour?
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Re: Is there a way to prevent (re)protonation during conformer generation?

Stefano Forli
Hi,
as far as I know, the current version of OB doesn't handle gracefully stereogenic centers
in rings, but I believe the version in the GitHub repo (that's going likely to be the next
stable one) should do that.

About protonation states, you could try to use the '-p' option to set the pH you want to
simulate. Although, I have to say that the stable version (2.3.2) is known to have
problems with that.

A solution would be to download the latest code from GitHub and compile it yourself[1], if
you know how to do it.


S


[1] https://openbabel.org/docs/dev/Installation/install.html#compiling-open-babel

On 03/08/2016 05:08 AM, mirix wrote:

> I am generating 3D structures from canonical SMILES and I am facing several
> issues.
>
> The first is that OpenBabel does not seem to be able to produce structures
> with the right sterochemistry in certain cases (even if it is explicitly
> indicated in the SMILES). As far as I can tell, this happens with fused
> rings where both (contiguous) shared atoms are sterocenters.
>
> The workaround I found is converting the SMILES to mol2 with Balloon
> (because Omega2 fails with a few of them) and then:
>
> obabel ${ligandid}.mol2 -O ${ligandid}.sdf --conformer --nconf 200 --score
> energy --writeconformers
>
> The problem is that obabel seems to reprotonate certain functional groups
> (such as carboxylic acids which are deprotonated on purpose). Is there a way
> to prevent such behaviour?
>
>
>
>
> --
> View this message in context: http://forums.openbabel.org/Is-there-a-way-to-prevent-re-protonation-during-conformer-generation-tp4659206.html
> Sent from the General discussion mailing list archive at Nabble.com.
>
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--

  Stefano Forli, PhD

  Assistant Professor of Integrative
  Structural and Computational Biology,
  Molecular Graphics Laboratory

  Dept. of Integrative Structural
   and Computational Biology, MB-112A
  The Scripps Research Institute
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Re: Is there a way to prevent (re)protonation during conformer generation?

mirix
Thanks Stefano. Yes, I have compiled OB several times. I will try the development version then.

Yes, the stable version tends to reduce aromatic rings if you use -p7.4 along with --conformer. Otherwise, -p works fine in most instances.

Cheers,

Miro

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Re: Is there a way to prevent (re)protonation during conformer generation?

mirix
In reply to this post by Stefano Forli
Hello,

I just wanted to report that the development version of obgen (Open Babel 2.3.90 -- Mar 11 2016 -- 14:28:36) still has problems with assigning the stereochemistry of certain fused rings.

Kind regards,

Miro