[gmx-users] MM dihedral scanning

[Mohsen Ramezanpour]

On Thu, Jan 12, 2017 at 4:24 PM, Justin Lemkul <jalemkul at vt.edu> wrote:

>
>
> On 1/12/17 3:18 PM, Mohsen Ramezanpour wrote:
>
>> Dear Gromacs users,
>>
>> For parameterization of a molecule in Charmm36, I have got the QM scanning
>> and partial charges from GAMMP server. However, the fitted parameters are
>> not good enough.
>>
>
> That's very surprising.  What's wrong with what GAAMP gave you?
>
The dihedral has two local minima in both QM and fitted ones both from
GAAMP. The angle for the minima are okay but the corresponding depths are
not.
In fact, the depth for the first local minimum is larger than second one in
QM, while the situation is reverse in MM profile with fitted parameters.
This makes the dihedral to be more (statistically) in wrong angle (in local
minimum which is not the most favourable one).
GAAMP, unfortunately, did not work well with my case (some critical partial
charges and critical dihedrals).


> I decided to do the MM scanning and try to get better parameters for the
>> dihedral.
>>
>> Unfortunately, I do not have any experience with this part, and I could
>> not
>> find any tutorial for how to do this in Gromacs.
>> I was wondering if you are aware of any tutorial which could help me to
>> overcome this challenging step.
>>
>>
> Tutorial (CGenFF theory is the same as CHARMM, by design):
> http://mackerell.umaryland.edu/~kenno/cgenff/download.php#tutor
>
> Fitting program and other resources:
> http://mackerell.umaryland.edu/~kenno/lsfitpar/
> http://mackerell.umaryland.edu/ff_dev.shtml
>
> Obviously, these are all CHARMM-centric approaches and frankly the modules
> within CHARMM make parametrization rather straightforward (not "easy," mind
> you, but straightforward).  Since I began working with CHARMM, it has
> become indispensable in my daily routine.
>
> If you want to do things in GROMACS, the main issue is that you will have
> to do MM scans in a more manual fashion, by restraining the target
> dihedrals (very strongly) in a series of configurations (typically at
> intervals of 15 degrees over a full rotation) while allowing the rest of
> the molecule to relax to match the QM.

If I got it right, I must do EM on the molecule while only the desired
dihedral is fixed in a specific angle. Which aspect should match with QM?
If you mean structurally, what is the criteria for matching (RMSD?.)?



  Deactivate the restraint, obtain the potential energy of the molecule via
> mdrun -rerun and plot as a function of the dihedral.

This should be a zero step EM, right? The molecule should not be allowed to
change its conformation.

  A bit of shell scripting and careful topology modification and this can
> be done.
>

Two more questions on this part:
1) I am using the QM scanning data and partial charges from GAAMP. When I
do this MM scanning, do I need to exclude any 1-4 interactions or I can
behave this dihedral as other dihedrals?
2) this dihedral is part of a lipid.
Do I need to do these on only "one Lipid in vacuum"  or
OR
on all lipids in "a bilayer in vacuum" or in a "bilayer in solvent"

I think it should be  "one Lipid in vacuum".

>
> -Justin
>
> There are three parts of molecule which I am interested in its dihedral
>> parameters that I am stuck in it for a while:
>> 1) (*2,2-Diethyl-1,3-dioxolane*)
>> http://www.chemspider.com/Chemical-Structure.217102.html?
>> rid=378be046-1c14-4bce-ac46-6591776f7e08
>>
>> dihedrals of O-C-CH2-CH3
>>
>> 2) (DIMETHYLPROPYLAMINE)
>> http://www.chemspider.com/Chemical-Structure.55178.html?rid=
>> 16e49844-d25d-48c8-b1b5-89fb2f9372bd
>>
>> dihedral of CH3-N-CH2-CH2
>>
>> Many thanks in advance for any suggestion.
>>
>> Cheers
>> Mohsen
>>
>>
> --
> ==================================================
>
> Justin A. Lemkul, Ph.D.
> Ruth L. Kirschstein NRSA Postdoctoral Fellow
>
> Department of Pharmaceutical Sciences
> School of Pharmacy
> Health Sciences Facility II, Room 629
> University of Maryland, Baltimore
> 20 Penn St.
> Baltimore, MD 21201
>
> jalemkul at outerbanks.umaryland.edu | (410) 706-7441
> http://mackerell.umaryland.edu/~jalemkul
>
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