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

[lazaro monteserin]

I thought this approach initially because I will refine the calculations
later at DFT level. What do you think?

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