ADL: Ligand docking to MD ensemble

James Starlight jmsstarlight at gmail.com
Wed Apr 9 07:33:29 PDT 2014


Parker,

thanks for suggestions! But are there any possibilities to define ensemble
instead of single receptor's conformation as dcd or in nrm-like format in
Vina's conf file (I've seen such in GOLD) ?

By the way also I've forced with the problem during processing of my
receptor.pdbqt. I've made pdbqt from the charmm-format pdb using ADT but
after processing conf file in Vina I've received error something like
"Atomtype CE not found" How I can convert all atom names to autodock-like
format ?

James


2014-04-09 16:40 GMT+04:00 de Waal, Parker <Parker.DeWaal at vai.org>:

> Ahh,
>
> I misunderstood the question. I suppose to identify high affinity
> conformations you could start by taking evenly spaced snapshots of your
> simulation every 100 ps or so. Then You could dock your ligand into each
> conformation and determine which conformations have a relative binding
> affinity. Using this you could then try to determine the characteristics of
> those snapshots with higher binding affinities and how they differ from
> snapshots with lower binding affinities and perform some PCA to quantify.
> After you could search through your trajectory for frames with similar
> characteristics to those determined by your PCA and you should be able to
> narrow down your search.
>
> Alternatively... starting from your simulated apo protein I would simply
> dock your ligand into the binding site and run a ligand bound simulation.
> That would probably provide you with a more accurate answer than a static
> binding.
>
> Best,
> Parker
>
> -----Original Message-----
> From: autodock-bounces at scripps.edu [mailto:autodock-bounces at scripps.edu]
> On Behalf Of James Starlight
> Sent: Wednesday, April 09, 2014 8:30 AM
> To: autodock at scripps.edu
> Subject: Re: ADL: Ligand docking to MD ensemble
>
> Hi Parker,
>
> I think I'm not need in MMPBSA because the only I need to dock my ligand
> to one of the conformation obtained as the result of the apo protein
> simulation. E.g random selected conformation from apo trajectory can be
> with the locked active site if the docking will be accompanied with the
> sterical clashes :) So i need simple algorithm of the selection the most
> (sterically) appropriated (defining active site) conformation from the
> ensemble.
>
>
> James
>
>
> 2014-04-09 16:22 GMT+04:00 de Waal, Parker <Parker.DeWaal at vai.org>:
>
> > Hi James,
> >
> > You might want to look into MMPBSA or MMGBSA calculations. Using these
> > methods you can compute relative binding energies for various
> > conformations throughout your simulation which will probably be more
> > accurate than the internal auto dock calculations if configured
> correctly.
> >
> > Best,
> > Parker
> >
> > -----Original Message-----
> > From: autodock-bounces at scripps.edu
> > [mailto:autodock-bounces at scripps.edu]
> > On Behalf Of James Starlight
> > Sent: Wednesday, April 09, 2014 8:16 AM
> > To: autodock at scripps.edu
> > Subject: ADL: Ligand docking to MD ensemble
> >
> > Dear AutoDock users!
> >
> >
> > I'm looking for the Autodock tutorial where I could  find brief
> > description of how protein flexibility from the MD simulation could be
> > take into account during the docking run. For instance I have ligand
> > and ensemble of conformations  in dcd or pdb format corresponded to
> > the fragment of my MD trajectory. Now I'd like to dock my ligand to
> > each of that conformation in its pre-defined active site and find to
> > what conformation from ensemble my ligand has higher affinity. I'll be
> > thankful for any suggestions.
> >
> > Thanks for suggestions,
> >
> > James
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