From: Aaron Larsen (alarsen_at_molbio.mgh.harvard.edu)
Date: Thu Jun 18 2015 - 14:57:16 CDT

That's an excellent point to be aware of. In this case, there are ortho
substituents which I will need to be cautious of. This may explain what I
am seeing.

On Thu, Jun 18, 2015 at 3:37 PM, Mayne, Christopher G <cmayne2_at_illinois.edu>
wrote:

> One other note to make...if the amino group is forced to rotate out of
> plane, e.g., steric clash with an ortho substituent, as the electron pair
> of the amino decouples from the pi system of the aromatic ring, the
> geometry is expected to distort more towards tetrahedral. The extreme
> being an animo group that is perpendicular to the ring system should be
> tetrahedral. Under these scenarios, the CHARMM force field is unable to
> represent the changing preference in geometry.
>
> Regards,
> Christopher Mayne
>
>
>
> On Jun 18, 2015, at 2:27 PM, Aaron Larsen wrote:
>
> Hi Christopher,
>
> I've measured the deflection of the amino group from a planar geometry
> and it seems that it's somewhat intermediate between trigonal planar and
> tetrahedral, which might be a reasonable expectation. I have not compared
> it statistically to a well parameterized amino-containing nucleobase,
> however. I have begun paying special attention to the angle and dihedral
> force constants for the other ring bonds and I believe that if I find cause
> to strengthen these associations, it may help 'calm down' the aminos. I'll
> let you know if I make any more progress.
>
> Best,
> Aaron
>
> On Thu, Jun 18, 2015 at 2:26 PM, Mayne, Christopher G <
> cmayne2_at_illinois.edu> wrote:
>
>> Aaron,
>>
>> I'm cc'ing VMD-L so that others can benefit from our discussion.
>>
>> One of my colleagues in our labs has observed this behavior with a
>> molecule that looks similar to guanine. I have tested the geometry
>> optimization setup using ffTK for aniline, 1-naphthylamine, and a
>> substructure of our guanine-like molecule, and I cannot reproduce the
>> distortion towards tetrahedral character for exocyclic amines conjugated to
>> the aromatic system.
>>
>> Have you made any progress on these molecules?
>>
>> Regards,
>> Christopher Mayne
>>
>> On Jun 12, 2015, at 10:48 AM, Aaron Larsen wrote:
>>
>> Hi Christopher,
>>
>> Of course. The nucleobase geometry before the opt. geometry step was
>> totally planar with respect to the aminos, exactly as you would expect. The
>> output from Gaussian featured the same aminos but now with tetrahedral
>> geometry with respect to the aminos. I corrected the geometry manually in
>> the resulting pdb files, hoping that would be sufficient to continue.
>> However, when I run simulations with the fully parameterized molecule, I
>> continue to see the amino groups adopt a tetrahedral geometry. In fact, the
>> heterocycles seem to distort slightly from a planar geometry overall. This
>> indicates to me that perhaps the torsions or angle force constants are too
>> low.
>>
>> Any advice on how to correct this issue would be most appreciated.
>>
>> Best,
>> Aaron
>>
>> On Fri, Jun 12, 2015 at 11:18 AM, Mayne, Christopher G <
>> cmayne2_at_illinois.edu> wrote:
>>
>>> Aaron,
>>>
>>> I'm not sure what you mean by:
>>> > FFTK seems intent on treating these aminos as tetrahedral in geometry
>>>
>>>
>>> Can you expand on where the perceived problems with geometry are
>>> occurring?
>>>
>>> Regards,
>>> Christopher Mayne
>>>
>>>
>>> On Jun 12, 2015, at 8:03 AM, Aaron Larsen wrote:
>>>
>>> > Hello VMD users,
>>> >
>>> >
>>> > I'm in the middle of parameterizing a bunch of nucleobase like
>>> molecules with the FFTK. Some of them are decorated with aminos. These
>>> amino groups SHOULD be planar in geometry, reflecting the aromatic nature
>>> of the heterocycles to which they are attached. However, FFTK seems intent
>>> on treating these aminos as tetrahedral in geometry. It seems that there
>>> should be a simple work around for this. Would anyone have any suggestions
>>> on how to proceed?
>>> >
>>> > It would be preferable if the solution did not involve starting over
>>> from the Molefacture step.
>>> >
>>> > Best,
>>> > Aaron
>>>
>>>
>>
>>
>> --
>> Aaron Larsen, Ph.D.
>> Harvard University Department of Chemistry and Chemical Biology
>> Harvard Medical School Department of Genetics
>> E-mail: alarsen_at_molbio.mgh.harvard.edu
>> Mobile: 617-319-3782
>> FAX: 617-643-3328
>>
>>
>>
>
>
> --
> Aaron Larsen, Ph.D.
> Harvard University Department of Chemistry and Chemical Biology
> Harvard Medical School Department of Genetics
> E-mail: alarsen_at_molbio.mgh.harvard.edu
> Mobile: 617-319-3782
> FAX: 617-643-3328
>
>
>

-- 
Aaron Larsen, Ph.D.
Harvard University Department of Chemistry and Chemical Biology
Harvard Medical School Department of Genetics
E-mail: alarsen_at_molbio.mgh.harvard.edu
Mobile: 617-319-3782
FAX: 617-643-3328