[Dock-fans] Critical points docking

[Scott Brozell]

Hi,

It seems that there is a problem with critical points.
I am shopping around for a simple test case.

Scott

On Mon, 17 Mar 2008, Dmitry Osolodkin wrote:

> Scott Brozell wrote:
> > Yes the sphere file format is correct according to
> > http://dock.compbio.ucsf.edu/DOCK_6/dock6_manual.htm#SphgenCriticalPoints
> > Yes I see no reason to rebuild grids.
> >
> > Dock 6.2 contains code to read and check critical points.
> > It does not appear to be obviously wrong.
> > However, there are no tests or examples that use critical points.
> > I'm contacting other developers for the status of critical points.
> >
> > In the mean time you could try the alternative mentioned in
> > http://dock.compbio.ucsf.edu/DOCK_6/dock6_manual.htm#CriticalPoints
> > to determine whether your system is conducive to critical points.
> >   
> Okay, I have deleted some critical points which seem unreasonable to use 
> for docking. Nevertheless, I haven't rebuilt the grids, so in the 
> docking run I have used a rather big box which only had spheres in one 
> corner. The best-scored orientation of the ligand was rather reasonable, 
> but the minimal distance between my ligand and critical points was about 
> 6 Ã
. This distance seems unreasonable. See 
> http://qsar.chem.msu.ru/~dmitry_o/cp.png (spheres are shown as balls and 
> transparent spacefill, critical spheres are orange, and the best scored 
> orientation is ball-and-stick (a part of it is hidden behind the spheres)).
> Moreover, the primary conformations are positioned in the different 
> places of the box, and this positions are not directed by spheres. As 
> far as I understand the DOCK concept, it should suggest only 
> orientations defined by spheres, so if there is an empty box region 
> without the spheres and receptor atoms, there shouldn't be any ligand 
> atoms in this region. But in my case there are a lot of ligand 
> orientations which are not intersected with any sphere. Maybe the reason 
> is that my molecule is small and no anchor is defined during docking?
> Third, after activation of the chemical matching feature on the same 
> four spheres, there were no difference between results obtained with 
> critical points, without critical points and with chemical matching. Is 
> it an algorithm problem?