[gmx-users] about correct methodology to run MD of small molecule in gromacs

[Justin Lemkul]

On 4/19/20 4:25 PM, lazaro monteserin wrote:
> I thought this approach initially because I will refine the calculations
> later at DFT level. What do you think?

If you need a QM reference state for subsequent geometry refinement, 
just generate the QM-optimized geometry and start your calculations from 
that. You can then do an energy minimization with the force field to 
determine how well the molecular mechanics approximation agrees with QM 
(perhaps not very well as most nucleic acid force fields have not used 
DFT methods in their derivation).

-Justin

> On Sun, Apr 19, 2020 at 5:17 PM Justin Lemkul <jalemkul at vt.edu> wrote:
>
>>
>> On 4/19/20 4:12 PM, lazaro monteserin wrote:
>>> Dear Dr. Lemkul you are completely right. But then how could I approach
>>> this problem to get an answer at the end that make sense?
>> What is the purpose of requiring that the simulation start from the most
>> stable vacuum conformation? There are very few rotatable bonds in a
>> nucleoside and they are likely capable of fairly exhaustive sampling in
>> water, anyway. The force field isn't designed for vacuum so anything you
>> generate is likely to either be irrelevant in water or otherwise easily
>> accessible in water in the first place.
>>
>> -Justin
>>
>>> On Sun, Apr 19, 2020 at 4:39 PM Justin Lemkul <jalemkul at vt.edu> wrote:
>>>
>>>> On 4/18/20 7:39 PM, lazaro monteserin wrote:
>>>>> Dear Gromacs users,
>>>>>
>>>>> As I have referred before I am simulating small molecules (nucleosides)
>>>>> (around 33 atoms) in vacuum in Gromacs. When I do the simulations at
>> the
>>>>> end I want to select the most stable structure from the trajectory for
>>>> the
>>>>> next steps.
>>>>>
>>>>> What would be the best methodology to use to run a molecular dynamics
>> for
>>>>> this?:
>>>>>
>>>>> 1) Run an anneling and collect the different frames for the trajectory
>>>> and
>>>>> then at the end analyze the RSMD, free energy and maybe do clustering
>> for
>>>>> the different frames to select the most stable structure?
>>>> How do you propose to compute the conformational free energy? Note also
>>>> that no biomolecular force field is validated for use in the gas phase,
>>>> so the balance of conformational sampling has no guarantee of being
>>>> physically meaningful.
>>>>
>>>>> 2) Do an umbrella anneling similar to the Gromacs tutorial 3"umbrella
>>>>> sampling"?, the only problem here is that I want all dihedral angles to
>>>>> rotate and I do not know how to do this.
>>>> You can enforce dihedral rotation with the pull code, but the tutorial
>>>> has little use here aside from general concepts.
>>>>
>>>>> 3) Do a procedure similar to tutorial 6 "Free energy of solvation" in
>>>> which
>>>>> I generate the free energy from different lambda values from
>> consecutive
>>>>> simulations.
>>>> The tutorial is for decoupling a solute from water. You have a molecule
>>>> in vacuum. The only thing to decouple is the molecule itself, which will
>>>> give you an annihilated, physically nonsensical structure.
>>>>
>>>> -Justin
>>>>
>>>> --
>>>> ==================================================
>>>>
>>>> Justin A. Lemkul, Ph.D.
>>>> Assistant Professor
>>>> Office: 301 Fralin Hall
>>>> Lab: 303 Engel Hall
>>>>
>>>> Virginia Tech Department of Biochemistry
>>>> 340 West Campus Dr.
>>>> Blacksburg, VA 24061
>>>>
>>>> jalemkul at vt.edu | (540) 231-3129
>>>> http://www.thelemkullab.com
>>>>
>>>> ==================================================
>>>>
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>> --
>> ==================================================
>>
>> Justin A. Lemkul, Ph.D.
>> Assistant Professor
>> Office: 301 Fralin Hall
>> Lab: 303 Engel Hall
>>
>> Virginia Tech Department of Biochemistry
>> 340 West Campus Dr.
>> Blacksburg, VA 24061
>>
>> jalemkul at vt.edu | (540) 231-3129
>> http://www.thelemkullab.com
>>
>> ==================================================
>>
>> --
>> Gromacs Users mailing list
>>
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-- 
==================================================

Justin A. Lemkul, Ph.D.
Assistant Professor
Office: 301 Fralin Hall
Lab: 303 Engel Hall

Virginia Tech Department of Biochemistry
340 West Campus Dr.
Blacksburg, VA 24061

jalemkul at vt.edu | (540) 231-3129
http://www.thelemkullab.com

==================================================