ADL: Automating the Autodock

Jack Shultz jshultz at
Sat Apr 4 19:31:41 PDT 2009

Thanks Mark. That's some new material for me. I need to read about
these studies using B-Factor.


On Sat, Apr 4, 2009 at 3:35 AM,  <mswingle at> wrote:
> ----- Original Message -----
> From: Jack Shultz <jshultz at>
> Date: Friday, April 3, 2009 1:13 pm
> Subject: Re: ADL: Automating the Autodock
> To: autodock at, Riad Schulz <rschulz at>
>> Hello,
>> I am considering an experimental design that would perform virtual
>> screening using flexible receptors. I've already setup a good system
>> using the mgltools scripts. Now I am considering the flexible
>> receptors. When you prepare a flexible receptor you need to specify
>> which residues should be flexible. I am wondering if there are any
>> approaches to picking these receptors that would lend themselves to
>> automation.
>> Jack
> Jack,
> If you just mean automating the preparation when the flexible residues are user-supplied,
> there is a python script that comes with ADT that does that. Most likely, though, you're
> looking for a way to automate the identification of which residues should be made flexible.
> I don't think that there are any clear-cut methods for doing this unless you have a variety
> of different experimental structures available for the receptor in question or you're willing
> to run MD simulations.
> There have been attempts to predict flexible regions from the amino acid sequence (see
> e.g. ). I'm not that familiar with the
> literature but, IIRC, most of these studies use B-factors as a proxy for flexibility, which
> IMHO is a somewhat dubious assumption to make except for higher resolution structures.
> The other thing to consider is that we are not so much interested in residues that are
> inherently "jittery" in a given structure but rather those which may switch to a
> conformation that differs from that in the available structure. It is certainly possible
> (maybe even probable) that a residue involved in ligand binding could take on different
> highly stable (i.e. presumably low B-factor) conformations when different ligands are
> bound to the receptor. Thus, a low B-factor observed in one structure does not necessarily
> mean that the residue wouldn't switch to a new conformation in a different complex.
> OTOH a high B-factor might imply a predilection for changing conformation that would be
> useful to model during docking.
> If I were going to use B-factors as selection criterion, I think it would probably be best to
> take them from structures of unliganded receptors at ~2.5A resolution or better (B's can
> soak up a lot of model errors during refinement and should be viewed skeptically in low
> resolution structures). Also, they should probably be normalized in some fashion since B's
> are influenced by the resolution, the refinement protocols, and the crystal packing. It
> might also be useful to try to fit a TLS (translation libration screw-axis) model to the B's to
> try to separate out large-scale anisotropic motions of the whole receptor or domains from
> local motions (see e.g. ).
> Other considerations would include the type of residue (lys, arg, glu e.g. are notorious) and
> it's environment (solvent accessibility, h-bonding etc.).
> Hope this helps.
> Regards,
> Mark
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