[gmx-users] MM dihedral scanning

[Mohsen Ramezanpour]

On Thu, Jan 12, 2017 at 8:36 PM, Justin Lemkul <jalemkul at vt.edu> wrote:

>
>
> On 1/12/17 10:21 PM, Mohsen Ramezanpour wrote:
>
>> On Thu, Jan 12, 2017 at 6:31 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>>
>>
>>>
>>> On 1/12/17 7:47 PM, Mohsen Ramezanpour wrote:
>>>
>>> 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?.)?
>>>>
>>>>
>>>> "Match" in this case means "treat equivalently," therefore only one
>>> constraint (restraint in the MM) should be applied while allowing the
>>> rest
>>> of the molecule to relax freely.  You do have a difficult case because
>>> each
>>> of your molecules is symmetric; this means the same dihedral term is
>>> affecting multiple torsions.
>>>
>>> So, probably I should 4 dihedrals and try to optimize all at once?!(
>> because all 4 dihedrals of O-C-CH2-CH3 seems equivalent to me). Am I
>> right?
>>
>>
> No, there are 2 O-C-CH2-CH3 dihedrals, not 4.
>

How come? :-)  there are two ethyls and two oxygens in the ring. Each ethyl
forms two dihedrals (one with each oxygen).
Thus, there would be 4 dihedrals.  And all of these 4 should be equivalent.

>
>
>>>
>>>
>>>>   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.
>>>>
>>>>
>>>> No, a zero-step MD.  EM actually changes the coordinates before step
>>> zero.
>>>
>>>   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?
>>>>
>>>>
>>> 1-4 interactions are always at full strength in CHARMM.
>>>
>>> 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".
>>>>
>>>>
>>>> One model compound in vacuum, from which you will construct the lipid.
>>>
>>> How if this compound (which is small part of the lipid) is charged?
>> Should
>> it be still in vacuum?
>>
>
> Yes.  The fact that a molecule is irrelevant except for when considering
> the dipole moment.
>
> Is there any specific consideration to be made in zero-step MD? e.g. a big
>> simulation box or specific parameter in .mdp file?
>>
>>
> Infinite cutoffs, no PBC.
>
> -Justin
>
>
> --
> ==================================================
>
> 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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