[Chimera-users] chimera for Amber9

[Elaine Meng]

Hi Francesco,
There is a Dock Prep tool in Chimera: it cleans up the receptor (or  
ligand) structure, adds hydrogens, associates atoms with partial  
charges (Amber for standard residues, Antechamber calculations for  
nonstandard), and writes it out in Mol2 format.

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

However, it does not do anything to help find binding sites or to  
divide up a very large structure.  It is not involved in the surface  
and sphere calculation steps.  In the future we would like to better  
integrate Chimera with those steps, but it hasn't been done yet.

Using the dock-related programs, I imagine you would calculate sets of  
spheres that fill each large pocket of the protein, then calculate a  
scoring grid for each pocket and dock separately to the different  
pockets (as suggested by Dr Brozell).  The process would be similar to  
what is shown in the dock tutorials, just done multiple times for the  
different pockets.

There are several separate tools or web servers that you can use to try  
to identify pockets if they are not already obvious.  For example, the  
Surfnet tool in Chimera:
http://www.cgl.ucsf.edu/chimera/docs/ContributedSoftware/surfnet/ 
surfnet.html
or the CASTp web server:
http://sts.bioengr.uic.edu/castp/

I hope this helps,
Elaine
-----
Elaine C. Meng, Ph.D.                          meng at cgl.ucsf.edu
UCSF Computer Graphics Lab and Babbitt Lab
Department of Pharmaceutical Chemistry
University of California, San Francisco
                      http://www.cgl.ucsf.edu/home/meng/index.html


On Oct 2, 2007, at 3:12 AM, Francesco Pietra wrote:

> Hi Elaine:
> That you mention was wonderful discovery.
>
> Coming closer to my work: What I want to do at the moment is examining  
> if Dock
> can identify how certain natural products (lipophilic molecules of  
> about 180
> first-row atoms) interact with a large protein. I know experimentally  
> that
> there is interaction, nearly surely with the protein itself and not  
> merely a
> destruction of the bilayer. Though, I have no idea about the protein  
> region
> responsible.
>
> I have already carried out a conformational search for my natural  
> products by
> simulated annealing with an algorithm that calls Amber9. Parameter and
> coordinate files for Amber9 were built with Antechamber. X-ray  
> diffraction data
> at medium resolution for the protein are available.
>
> The tutorials on DOCK does not consider take such a problem (the  
> tutorial
> starts from a protein-ligand complex elucidated by X-ray diffraction).
> Professor Brozell suggested that the size of the protein may put a  
> practical
> limit on the size of Dock's grid, though, one approach would be to  
> divide and
> conquer the big protein binding sites into subsets that would be  
> processed
> separately.
>
> My question is: can Chimera help such preparation of the protein for  
> docking?
>
> Thanks
> francesco
>