[gmx-users] MM dihedral scanning

Fri Jan 13 04:21:25 CET 2017

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?

>
>
>>
>>   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?
Is there any specific consideration to be made in zero-step MD? e.g. a big
simulation box or specific parameter in .mdp file?

Thanks Justin for your comments.

>
> -Justin
>
>
>
>>> -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
>>>
>>> ==================================================
>>> --
>>> Gromacs Users mailing list
>>>
>>> * Please search the archive at http://www.gromacs.org/Support
>>> /Mailing_Lists/GMX-Users_List before posting!
>>>
>>> * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
>>>
>>> * For (un)subscribe requests visit
>>> https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or
>>> send a mail to gmx-users-request at gromacs.org.
>>>
>>>
>>
>>
>>
> --
> ==================================================
>
> 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
>
> ==================================================
> --
> Gromacs Users mailing list
>
> * Please search the archive at http://www.gromacs.org/Support
> /Mailing_Lists/GMX-Users_List before posting!
>
> * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
>
> * For (un)subscribe requests visit
> https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or
> send a mail to gmx-users-request at gromacs.org.
>

-- 
*Rewards work better than punishment ...*