[Dock-fans] docking protocol

[Scott Brozell]

Hi,

On Thu, 8 May 2008, John J. Irwin wrote:

> You might want to contact the authors of that paper at U Maryland for 
> advice.
> 
> Jerry Parks wrote:
> >
> > I'm interested in performing normalized vdW attractive energy scoring as
> > described in J. Med. Chem. 2005, 48, 4586-4595. Can Dock 6.2 do this
> > automatically, or should I just write a script to extract the vdW
> > attractive energy from the output and normalize it myself?

There is no automatic support for this in DOCK.

> > Could you comment on the energy cutoff distance in grid.in? Is it
> > reasonable to use a finite cutoff (rather than the 9999 used in the
> > tutorial). Is there any general rule for selecting the cutoff besides
> > systematically testing the convergence for various cutoff distances? How
> > about max_orientations?

The default value of 10
http://dock.compbio.ucsf.edu/DOCK_6/dock6_manual.htm#GridEnergyScoring
is the one used in the publication, p507
http://dock.compbio.ucsf.edu/DOCK_6/dock6_manual.htm#MengetalJCompChem1992
But was probably chosen for computational time reasons.
Now speed is unlikely to be an issue, and the whole receptor
might as well be used.

> > Also, is there any sort of general guideline for choosing the "right"
> > number of spheres? My binding site is defined by three residues that are
> > known to be important from mutation studies. I selected spheres within 8
> > Angstroms of those three residues, and then augmented those with
> > additional spheres corresponding to xray waters in roughly the same
> > region. There are a total of about 40 spheres, and the coverage of the
> > binding pocket looks fairly complete to me. Does this sound sufficient?
> > Could this be too many spheres?

Ensure that the active site(s) are covered.
Probably sufficient.
Probably not, too many spheres is usually relative to computational resources
or to calculations focused on specific regions of the receptor.

It would be good to hear from others on these issues.

Scott