[Dock-fans] Docking polypeptides

[John J. Irwin]

Hi Francesco

In my experience, DOCK works best with non-peptide small molecules. One
reason is that peptides are generally big and floppy. Once you get past
7 or 8 rotatable bonds, it rapidly becomes very expensive to sample
conformational space. A second reason why peptides are difficult for
DOCK is due to the anchor-and-grow concept, that starts from a rigid
fragment (e.g. Phe/Tyr/Trp/His ring).  I'm not saying it is impossible,
but you have at least two effects working against you on an already hard
problem. Past about 4 AA residues (unless they are all Gly or Ala), I
wouldn't even bother trying, although I am sure some people are braver.

One way to work around the "anchor choice problem" and, at least in
part, the "conformational enumeration problem" is to use omega
(eyesopen.com) outside DOCK, turning off anchor-and-grow. This lets DOCK
use the entire molecule for orientation, side-stepping the rigid
fragment choice problem. Of course, you may need to let omega generate a
very large number of conformations, but it is good at that. Anyway, that
is how I would do it, for a small peptide (say up to 4 residues).  Some
problems in protein-peptide recognition may be reducible to the
recognition of 4 key residues.

Beyond 4 residues, I would suggest using one of the programs for
protein-protein docking that participated successfully in CAPRI
(http://capri.ebi.ac.uk/). There is a lot of information on that site
that can help you pick the program that will work best for your situation.

Good docking

John
UCSF DOCK Team

Francesco Pietra wrote:
> Any experience, published work, on docking large peptides onto
> proteins with DOCK? Besides docking non-peptide molecules, I would
> like to dock a large peptides onto the same protein. There are
> experimental data about the protein domain involved with one of these
> polypeptides, so that it would be a useful test.
>
> Thanks
> francesco pietra
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