[Dock-fans] Docking to Amber Correlation

Scott Brozell sbrozell at rci.rutgers.edu
Wed Jun 18 13:56:30 PDT 2014


Hi,

On Wed, Jun 18, 2014 at 05:14:15PM +0000, Daniel Graham wrote:
>     I am currently using the dock input parameters shown on the Rizzo tutorial, http://ringo.ams.sunysb.edu/index.php/2014_DOCK_tutorial_with_HIV_Protease .
>     I am currently participating in a docking study where we are using high throughput screening. I am screening millions of compounds using dock6's grid score function, however it yields too many hits to be useful. Is there a way I can be more selective?
> 

There are many approaches; see below for one. 
I'll let the tutorial writers make specific suggestions on their inputs.

>     ?We are also using Amber to perform detailed studies on molecules that show good potential, however some of my top dock scorers (-90 grid score) do not score as well as some of my average scorers (-40 grid score). It seems that after a molecule scores below -30 it might have potential. This presents an issue because Amber calculations take much longer and I don't want to have to go though thousands of compounds basically guessing about which ones may score well in Amber. Is there a way to generate grid scores that better reflect how the molecule will do in Amber?
> 

The general behavior that you state is typical.
One step between Dock grid score and full MD in Amber would be 
Dock Amber score which is MM-GB/SA rescoring.
The default input parameters for Dock Amber score could provide
enough Amber minimization and MD to allow a superior ligand screen
at a computational expense substantially more than grid score
but substantially less than full MD.

There are many caveats, but one important point is receptor preparation.
If i infer correctly that you have already fully prepared your receptor
for your full MD Amber calculations then you may have taken a big step
towards eliminating one source of error in Dock Amber score.
In addition, if you have specific knowledge about the receptor then a
non-default input file using the NAB atom expression could be useful.

For details see
http://dock.compbio.ucsf.edu/DOCK_6/dock6_manual.htm#AMBERScore
http://dock.compbio.ucsf.edu/DOCK_6/tutorials/amber_score/amber_score.htm

scott



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