[Dock-fans] dock -internal energy and grid score

Sudipto Mukherjee sudmukh at yahoo.com
Wed Feb 13 14:44:43 PST 2013


Hi Mary,

In addition to using SYBYL atom types instead of the amber/gaff types in the mol2 file, check the bond orders in the linker joining the two aromatic rings together. 

The DOCKPrep tool in Chimera is especially helpful in setting up molecules for docking.

http://www.cgl.ucsf.edu/chimera/docs/ContributedSoftware/dockprep/dockprep.html

http://dock.compbio.ucsf.edu/DOCK_6/tutorials/struct_prep/prepping_molecules.htm

 
Regards
Sudipto Mukherjee



________________________________
 From: Trent E. Balius <tbalius at aol.com>
To: maryvj1985 at gmail.com; dock-fans at docking.org 
Sent: Tuesday, February 12, 2013 10:21 AM
Subject: Re: [Dock-fans] dock -internal energy and grid score
 

Hi Mary,

Your mol2 file is not using the sybylatom types which is required for running DOCK 6.  The atom types are found in the 6 column of the mol2 file:

      1 C1          8.5412   23.1768   75.6369 ca      1  PIP        -0.1147
      2 C2         10.8735   24.3956   72.9188 ce      1  PIP        -0.0761

This should should be:

      1 C1          9.2120   23.4220   74.9170 C.ar      1 PIP     -0.1147
      2 C2         11.0610   25.0710   72.0800 C.2       1 PIP     -0.0761

I would suggest regenerating the mol2 files to use sybyl atom types.

You can see that when you rescore with a full MM energy function the the ligand internal, solvated energy (3.69) is more reasonable.

I think that the large internal energy value (499.31) is do to the atom type issue mentioned above.  

I hope this helps,

Trent


======================================
Trent E. Balius, PhD
Shoichet Lab – Dept. of Pharm Chem,
University of California, San Francisco
1700 4th Street
Box 2550
San Francisco, CA 94158 
Office: Byers Hall, Rm 509
URL: http://docking.org/~tbalius
======================================



-----Original Message-----
From: Mary Varughese <maryvj1985 at gmail.com>
To: Trent E. Balius <tbalius at aol.com>; dock-fans <dock-fans at docking.org>
Sent: Tue, Feb 12, 2013 12:16 am
Subject: Re: [Dock-fans] dock -internal energy and grid score

 

Sir,

Thank you very much. But would you please look at this output_scored.mol2 file obtained from amberscore. I use the default values in dock.in file of the tutorial. Your opinion on the values will be helpful to me.

"rigid_scored.mol2 from the gridscore and output_scored.mol2 from amberscore(using the  rigid_scored.mol2)"

Thanking you.

 
On Tue, Feb 12, 2013 at 1:07 AM, Trent E. Balius <tbalius at aol.com> wrote:

Hi Mary,
>
>Yes, I think that if the conformation seems reasonable to you, I would trust your intuition.  
>
>The 
DOCK internal energy is not the "true" internal energy since it does not 
include dihiderals, bonds, or the attractive through space terms.  
>
>You may want to re-score the conformation using a full Molecular Mechanics force field to get a more reasonable internal energy using for example Amber.  You could use AmberScore:
>
>http://dock.compbio.ucsf.edu/DOCK_6/dock6_manual.htm#AMBERScore 
>
>
>I hope this helps,
>Trent  
>
>
>
>======================================
>Trent E. Balius, PhD
>Shoichet Lab – Dept. of Pharm Chem,
>University of California, San Francisco
>1700 4th Street
>Box 2550
>San Francisco, CA 94158 
>Office: Byers Hall, Rm 509
>URL: http://docking.org/~tbalius
>======================================
>
>
>
>
> 
>-----Original Message-----
>From: Mary Varughese <maryvj1985 at gmail.com>
>
>To: Trent E. Balius <tbalius at aol.com>
>Sent: Mon, Feb 11, 2013 11:12 am
>Subject: Re: [Dock-fans] dock -internal energy and grid score
>
> 
>Sir,
> 
>So if the pose seems reasonable i can ignore the internal energy as high as 500 or above?
>What do you think about opting the conformation (on doing parallel run generating 5 conformations; all give the same high internal energy) having internal clashes.
> 
>Thank you very much sir for the reply.
>
> 
>On Mon, Feb 11, 2013 at 10:55 PM, Trent E. Balius <tbalius at aol.com> wrote:
>
>Hi Mary,
>>
>>The internal energy is just the repulsive vdw term and is used to prevent the molecule form clashing with itself.  This term is always positive and indicates that there are internal clashes.  Visualize the molecule's dock pose and see if the pose seams reasonable to you.  
>>
>>See manual: 
>>http://dock.compbio.ucsf.edu/DOCK_6/dock6_manual.htm#InternalEnergyCalculation   
>>
>>To perform a "single point" calculation, where dock just will calculate the energy between a pose (crystal or pergenerated) of ligand and receptor, use the following parameter combination. 
>>
>>orient_ligand                                                no
>>flexible_ligand                                              no
>>score_molecules                                          yes
>>minimize_ligand                                           no
>>
>>You may want to perform restrained minimization of your ligand to remove clashes:
>>
>>orient_ligand                                                no
>>flexible_ligand                                              no
>>score_molecules                                          yes
>>minimize_ligand                                           yes 
>>simplex_restraint_min                                   yes
>>
>>I hope this helps,
>>
>>Trent
>>
>>
>>======================================
>>Trent E. Balius, PhD
>>Shoichet Lab – Dept. of Pharm Chem,
>>University of California, San Francisco
>>1700 4th Street
>>Box 2550
>>San Francisco, CA 94158 
>>Office: Byers Hall, Rm 509
>>URL: http://docking.org/~tbalius
>>======================================
>>
>>
>>
>>
>>
>>-----Original Message-----
>>From: Mary Varughese <maryvj1985 at gmail.com>
>>To: dock-fans <dock-fans at docking.org>
>>Sent: Sun, Feb 10, 2013 9:08 pm
>>Subject: [Dock-fans] dock -internal energy and grid score
>>
>>
>>
>>Hi,
>>
>>I docked a ligand to a DNA. But its internal energy is very high about 500.
>>Could this conformation be used.?
>>Also i want to calculate the grid score of a particular conformation. 
>>So i dont want blind dock and dock in a particular region ; because with a radius as small as 4.0 itself i couldnt get the particular conformation i want.
>>Could i calculate dock score without allowing dock to decide the conformation itself, but calculate grid score of the conformation specified by me.
>>Please help me in this issue
>>
>>thanking you
>>-- 
>>Mary Varughese
>>Research Scholar
>>School of Pure and Applied Physics
>>Mahatma Gandhi University
>>India
>>
>>_______________________________________________
Dock-fans mailing list Dock-fans at docking.org http://mailman.docking.org/mailman/listinfo/dock-fans 
>
>
>-- 
>Mary Varughese
>Research Scholar
>School of Pure and Applied Physics
>Mahatma Gandhi University
>India
>


-- 
Mary Varughese
Research Scholar
School of Pure and Applied Physics
Mahatma Gandhi University
India

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