ADL: Ligand docking to MD ensemble

de Waal, Parker Parker.DeWaal at
Wed Apr 9 05:40:47 PDT 2014


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.


-----Original Message-----
From: autodock-bounces at [mailto:autodock-bounces at] On Behalf Of James Starlight
Sent: Wednesday, April 09, 2014 8:30 AM
To: autodock at
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.


2014-04-09 16:22 GMT+04:00 de Waal, Parker <Parker.DeWaal at>:

> 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 
> [mailto:autodock-bounces at]
> On Behalf Of James Starlight
> Sent: Wednesday, April 09, 2014 8:16 AM
> To: autodock at
> 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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