[gmx-users] [gmx-user] Autodock Vina Out use in gromacs MD

[Quin K]

Dear Proffesor Lemkul,

I have given below the MD RMSD for complex, and noted that Ligand is
getting detached again. When I viewed the trajectory on VMD it was
confirmed.  The ligand did not abruptly got dislodged instead it slowly
came out of binding pocket and started moving around after.
https://drive.google.com/file/d/1IBMU-8SzSgXVr_h9zyeVwNV7kQ4at8-S/view?usp=sharing

I know that following CGenFF tutorial and fixing the molecule and
reparameterization would be the correct thing to do however I lack time at
this moment.
I read the paper and went through the tutorial and it's some what of a
complex method to fix the parameters.
I was thinking if I should use a different force-field such as Gromos with
parameterization with ATB server.
I have already submitted the given molecule below for optimization in ATB
and the parameterization is now complete.
Other option is to use Amber force field. Kindly let me know what your
opinion on this.

Molecule
https://drive.google.com/file/d/1Ni8rUX4sH3aKaRhhXqCZr9w8VJVetCI7/view?usp=sharing

Interactions at binding site us DS Visualizer
https://drive.google.com/file/d/16EkWYDPDyTfkERiQgaOYo4XxYxqslOD0/view?usp=sharing

Also please let me know if you think the given interactions are enough to
keep the molecule at binding site for like 100ns?

Thank you in Advance!
Kind Regards
Q

On Tue, Dec 31, 2019 at 9:21 AM Justin Lemkul <jalemkul at vt.edu> wrote:

>
>
> On 12/30/19 1:51 PM, Quin K wrote:
> > Further to following email, is it OK to do an energy minimization with
> > Gaussian16 so the molecule is refined before MD simulation with Gromacs?
>
> What would be the purpose? A gas-phase optimized geometry has no
> relationship to the pose adopted by a molecule upon binding to its
> receptor.
>
> > If such an energy minimization is done should I use DFT ?
>
> Depends on the force field you're using. Most biomolecular force fields
> do not use DFT for most calculations. If this goes back to our original
> discussion about your CGenFF parameters, I beg you to follow the advice
> I already gave - read the CGenFF paper. It tells you the *exact* model
> chemistries you should use for everything to ensure compatibility with
> the CHARMM force field.
>
> > Would that affect the orientation at which molecule was docked with
> > protein?
>
> No, because the docking software changes the configuration.
>
> -Justin
>
> >
> > On Mon, Dec 30, 2019 at 8:35 PM Quin K <profiles.ke at gmail.com> wrote:
> >
> >> Hi
> >>
> >> I noted when I used Autodock vina for docking and used the converted
> back
> >> .mol2 file from .pdbqt format, there were a lot of changes in the
> molecule
> >> than the molecule I initially submitted to Vina for docking. Like the
> *atomic
> >> charges were different. *
> >> Is this normal? or is there a way to use the original DFT optimized
> >> molecule with current docking orientation of Vina output file??
> >> Also noted that there were missing atoms like hydrogens.
> >> Last time I tried this simulation the ligand got detached from binding
> >> site after like 20 ns. This could probably be a main reason for that
> >> because I never refined the molecule to adjust for changed charges etc.
> >>
> >> Kindly give your opinion
> >> Thanks!
> >> Regards!
> >>
>
> --
> ==================================================
>
> 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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