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

[Justin Lemkul]

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

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