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Androstenedione parameters
#25620 10/15/10 04:29 AM
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Manori Offline OP
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Dear charmmers,

I am going to parametrize a compound from androgen family namely androstenedione. I am going to adopt the cholesterol parameters for this compound. My question is how to get the parameters for the ketone oxygen attached to the benzene carbon in C3 and C17 positions. Is there any compound in the data bank that I could use for this purpose? It is grateful if anyone could give me a clue how to go about it.

Thank you very much

Manori

Re: Androstenedione parameters
Manori #25635 10/17/10 08:25 PM
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Steroids are (mostly) not aromatic, so I don't think you should be looking for oxygen double bonded to a "benzene" carbon. Any ketone might be a good starting point (subject to testing) for C17, while for C3, a ketone conjugated to a C=C double bond would probably be better as an initial model. Always keep in mind that your final results may well depend on how careful you are when defining a new molecule; be critical, and test your assumptions.


Rick Venable
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Re: Androstenedione parameters
rmv #25641 10/18/10 06:00 PM
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What Rick said. The most important model compound to be parameterized in this case would be butenone. We recently did phenylmethylketone (not released yet), which could be used as a source of initial guess parameters for butenone. But a potential energy scan around its rotatable bond would still be mandatory.

Brushing up on organic chemistry and basic math may also be helpful in preparation of the parametrization.

Re: Androstenedione parameters
rmv #25642 10/18/10 06:33 PM
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Manori Offline OP
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Dear rmv,

Thank you very much for the information. I have question. Why do you suggest C=C bond for C3 and not a any ketone for that too?

Manori

Re: Androstenedione parameters
Manori #25643 10/18/10 06:37 PM
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The partial charge distribution and the behavior of the single bond between the two double bonds are expected to differ from a ketone which is not conjugated to a double bond. Because of the ring constraint, cyclohexenone might be a better QM model for the A ring of a steroid.


Rick Venable
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Re: Androstenedione parameters
rmv #25646 10/19/10 05:29 PM
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Originally Posted By: rmv
cyclohexenone might be a better QM model for the A ring of a steroid.
True, but if we want to treat the "-enone" as a new functional group (which I think is justified), the best starting point would be butenone, where we can study this functional group in the absence of any external influences. That gives us generic (and hopefully transferable) parameters for enones; this is important for a general force field as we have learned by getting burned because of not doing the more generic cases first. After doing that, we can move on to cyclohexenone, then build the whole compound. If the speed of the parameterization process is more important than the precision, I think it would be safer to skip the cyclohexenone step than to skip the butenone step.

Re: Androstenedione parameters
Kenno #25660 10/21/10 05:57 PM
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Manori Offline OP
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Dear all,

Greatly thankful for both of you to clarify things. I have several more things bothering my mind,

1) I think the reason you are suggesting butenone because if I use Acetone (already in there) I couldn't get the dihedral angle. (Please explain whether I am correct) Can I start with Acetone to parametrize butenone?

2) Once you said that you already parametrized butenone. Do you think you can share these parameters with me?, then I can acknowledge you in our publications if any (anyway we will refer your papers)

3) Suppose I parametrize the butenone and obtain all the bond, angle, dihedral and charges, can I still use the rest of the cholesterol structure for my androstenedione.

4) Since cholesterol has different atom types how should I put it in the cgenff files.

Greatly appreciate your help.

Thank you very much

Manori

Last edited by Manori; 10/21/10 06:05 PM.
Re: Androstenedione parameters
Manori #25661 10/21/10 06:27 PM
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There's also the conjugation of the double bonds in the butenone system, which makes it quite distinct from acetone (or butanone).

Upon reflection, I now think that I would probably do QM calculations for cis- and trans-pentenone, with cis as a model for the conjugated C=C-C=O in a ring.

Also, some steroids do have an aromatic A ring, but those have an -OH at C3 (phenol analog).


Rick Venable
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Re: Androstenedione parameters
rmv #25664 10/21/10 08:45 PM
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Manori Offline OP
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Thanks rmv,

I understand that we have to parametrize double bond conjugated to ketone. Can I use the parameters from C7H7NO 3-acetylpyridine for this purpose because it has this property.

I am kind of getting confusing right now.

So, what you have suggested is,

starting from phenylmethylketone (actually Kenno has suggested this) as initial paras for butenone. And then parametrize cyclohexenone using butenone and the parametrize the final compound.

This is a very long process (may be I understood wrong). Do I have to do all the parameters or only the dihedral?

I would be grateful if Kenno or yourself could explain this to me in details step by step the process of parametrization.

This is a great help

Thanks both of you very much

Re: Androstenedione parameters
Manori #25665 10/21/10 10:10 PM
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I believe Kenno has a tutorial available for using CGenFF to add new molecules; see the "sticky" post at the top of this forum.

As I understand it, at the minimum you need to do a torsion scan of the central C-C single bond in butenone, to get dihedral parameters. Unless you have target data (expt), you could skip cyclohexenone.

I'm less certain about the charges, without some QM results as a guide.

I don't think the 3-acetylpyridine is a very good model for this.


Rick Venable
computational chemist

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