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

[lazaro monteserin]

Thank you very much Dr. Lemkul for the advice

On Sun, Apr 19, 2020 at 5:33 PM Justin Lemkul <jalemkul at vt.edu> wrote:

>
>
> 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
>
> ==================================================
>
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