ADL: Getting very similar docking results for multiple unrelated proteins (Vina)

Diogo Martins diogo.stmart at gmail.com
Sun Aug 9 12:58:00 PDT 2020


Hi, it's an artifact of the scoring function.

On Sun, Aug 9, 2020, 6:09 AM Matt K. <5xx7xx at gmail.com> wrote:

> Ok, then a follow up question: is this bias purely an artifact of the
> docking software and doesn't translate at all to the real world? Or do real
> world drugs also generally bind better if they are bigger?
> I'm asking because my screening is purely for repurposing already approved
> drugs, hence I don't care about drug-likeness, only which compounds will
> bind better in reality.
>
> On Sat, Aug 8, 2020 at 8:47 PM Diogo Martins <diogo.stmart at gmail.com>
> wrote:
>
> > Hello,
> >
> > It's good to be suspicious of docking scores. Larger molecules almost
> > always have better scores, maybe some form of normalization by size, such
> > as dividing the score by the number of atoms, could make them a little
> more
> > informative.
> >
> > Best regards,
> >
> >
> >
> >
> > On Sat, 8 Aug 2020 at 10:39, Matt K. <5xx7xx at gmail.com> wrote:
> >
> > > Hello everyone,
> > > I'm doing a screen using Vina and I got really suspicious when I got
> very
> > > similar results for three different sites on my protein, so I also ran
> > four
> > > unrelated proteins chosen at random from PDB, and results are also very
> > > similar. Most molecules are within the same percentile (or off by one
> or
> > > two percentiles) across all proteins.
> > >
> > > The molecules used for docking are from the ZINC15 database,
> specifically
> > > the "world" subset.
> https://zinc15.docking.org/substances/subsets/world/
> > > I've downloaded them in mol2 format, split into separate files using
> > > OpenBabel and prepared them using the MGLTools script
> > "prepare_ligand4.py"
> > > (this one here:
> > >
> > >
> >
> http://wind.isi.edu/marbles/assets/components/workflow_portal/users/lib/MGLTools/MGLToolsPckgs/AutoDockTools/Utilities24/prepare_ligand4.py
> > > )
> > > by using the "bonds_hydrogens" repair option.
> > >
> > > Protein preparation was done manually in Autodock Tools by deleting
> > > ligands, deleting water, adding all hydrogens, merging non-polar
> > hydrogens,
> > > adding Kollman charges, spreading charge deficit over all atoms in
> > residue,
> > > and choosing as macromolecule.
> > >
> > > Grid box for each protein was chosen manually with size usually
> 30x30x30
> > > angstrom set in each protein's primary binding site. Vina
> exhaustiveness
> > > was set to 12.
> > >
> > > What am I doing wrong here? Why are my results so similar across
> > unrelated
> > > proteins?
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> >
> >
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