[Dock-fans] Using Dock for "blind-docking" (Ben Keshet)

Zhong, Shijun szhong at rx.umaryland.edu
Tue Dec 4 09:53:06 PST 2007


Hi Ben,

We did use DOCK to identify binding site. Please see the paper:
Zhong, S.; MacKerell, A. D., Jr.
Binding Response: A Descriptor for Selecting Ligand Binding Site on Protein Surfaces
J. Chem. Inf. Model; (Article); 2007; 47(6); 2303-2315.
Hope it will be helpful for solving your problem.


Shijun Zhong


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Today's Topics:

   1. Using Dock for "blind-docking" (Ben Keshet)


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Message: 1
Date: Wed, 21 Nov 2007 10:37:42 -0500
From: "Ben Keshet" <keshet1 at umbc.edu>
Subject: [Dock-fans] Using Dock for "blind-docking"
To: <dock-fans at docking.org>
Message-ID: <200711211537.lALFbm9m026604 at smtp.umbc.edu>
Content-Type: text/plain;	charset="us-ascii"

I have followed recently the discussion here regarding the capabilities of
docking, when the binding site is unknown. It was written by a Dock-team
member (John Irwin) that:

"...We start with docking once we know the binding site. Are you asking if
docking can be used to rank binding sites by the likelihood that one binds a
particular ligand? Sure, why not, give it a try. But given the famously high
false positive rate of docking, the odds are against you".

I have a somewhat similar problem to Francesco's and would appreciate your
opinion.  

There is little information available about the binding site of my receptor,
but there are several attractive alternatives.  I am using Dock to bind
several inhibitors separately to each possible binding site, while I am
gradually increasing the radius of spheres to be included at each binding
site. 

For example, I (1) use "select_spheres" to select the spheres at 5A from the
possible site, (2) use Dock to predict the binding, and (3) expand the
spheres in the binding site to 8A, and repeat the docking (and increasing
radius and so on).  I stop when increasing the radius of spheres included
does not significantly change the binding pose.  

At the end I have ~5 possible binding configurations.  I then use
Amber_score to refine them and allow better judgment of the poses.
Eventually, I hope to be able to utilize this information to experimentally
test these binding sites (mutagenesis, modifications).   

Even though I think that this is not the original usage method that Dock was
designed for, does that seem as a reasonable approach or do you still
believe that the "odds are against me"? 

As Dock being my docking tool, I would greatly appreciate any thoughts and
comments you might have.

On another note - it says on your website that tutorials for "Rescoring DOCK
Runs with Solvation Scoring Functions" and "DOCK 3.5 Scoring Functions" will
be coming soon.  Do you have any estimation on when it will be available?  

Thanks you,
Ben Keshet





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