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

[Justin Lemkul]

On 1/4/20 1:17 PM, Quin K wrote:
> 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

It would be more useful to investigate which interactions are broken 
first or if there is a dihedral that rotates that leads to a 
conformational change in the ligand. RMSD tells you very little.

> 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.

The nice thing about CGenFF is it tells you where it thinks problems 
might be and how they score in terms of quality. Neither of the other 
options do that. You always need to validate a ligand topology. Black 
boxes might work well or they might work poorly. You just don't know.

> 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?

The Arg-ligand interaction should be pretty strong, but you have an 
identified "unfavorable" contact (which could be due to the rotameric 
state of Asn111 being suboptimal, and otherwise only nonpolar contacts. 
I wouldn't expect a very favorable binding free energy.

-Justin

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

Virginia Tech Department of Biochemistry
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jalemkul at vt.edu | (540) 231-3129
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