[Dock-fans] Fw: Re: Fw: Re: Fw: Re: Fwd: Re: Ligand Docking with DOCK6

Francesco Pietra chiendarret at yahoo.com
Wed Apr 23 01:34:02 PDT 2008


--- On Tue, 4/22/08, Scott Brozell <sbrozell at scripps.edu> wrote:

> From: Scott Brozell <sbrozell at scripps.edu>
> Subject: Re: Fw: Re: [Dock-fans] Fw: Re: Fw: Re: Fwd: Re:  Ligand Docking with DOCK6
> To: "Francesco Pietra" <chiendarret at yahoo.com>
> Cc: "dock-fans" <dock-fans at docking.org>
> Date: Tuesday, April 22, 2008, 10:12 AM
> Hi,

> There are several issues here.  First a clarification:
> 
> receptor_site_file
> and
> grid_score_grid_prefix
> are distinct.
> In all docking calculations (i.e., orient_ligand == yes)
> receptor_site_file defines the active site(s).
> grid_score_grid_prefix represents a special region of the
> receptor;
> special in that contact or energy scores can be computed
> very quickly
> for ligands that dock such that the whole ligand is in the
> region.
> Grids are not used with continuous score;
> grid_score_grid_prefix is not a Continuous Energy Score
> Parameter;
> with continuous score cont_score_rec_filename is the
> receptor.

OK. Sorry for having posted mixed continuous/grid scoring. However, in the computations, the two were treated separately, and in accordance with what you write above.

> 
> Second I am not sure exactly what you mean by points.
> It is best to quote verbatim input and output items.  Note
> that
> relating a .sph file to a showbox margin and Total number
> of grid points
> is only a crude way to gauge active sites and
> receptor region sizes.  Grids are not used with continuous
> score;
> showbox margin and Total number of grid points are
> irrelevant.

OK, sorry again as above. Please, see below for continuous docking with respect to the number of spheres.

> 
> Third if you are uneasy about blindly leaving a long
> calculation
> that is producing no output running then ramp up to a long
> calculation, perhaps starting with a scientifically useless
> calc.
> The main problem was memory consumption; the total number
> of spheres
> in the receptor_site_file is directly related to memory
> consumption:
> Take a receptor_site_file and delete half the spheres from
> it;
> if necessary patch up the number of spheres in the header:
> e.g.,
> cluster     1   number of spheres in cluster    12
> run dock measuring the memory usage;
> if the calculation is too long then stop it; repeat this
> procedure.
> Eventually, you will get to a quickly running dock calc
> (perhaps
> terminating without actually docking the ligand).
> After a couple of steps you will have a formula for memory
> use
> as a function of the total number of spheres and a feeling
> for
> computation time.

I have now carried out continuous docking serial runs (same *.in file as before) for the tree, same-family compounds already dealt with on present thread, and for which I have carried out biochemical experiments as to their interaction with the protein. Computations for two situations of 

sphere_select -i rec.sph -c protein_noH.pdb -a 3421 -3 radius_in_A

where 3421 is the strategic atom number where the sphere was centered. I use two values of the radius, 23A and 25A. In both cases the spheres (568 for 23A and 685 for 25A) represent satisfactorily the protein. The 568 spheres situation only leaves out protein loops that may safely be considered irrelevant to the docking.


For the 5-rings and 8-rings compounds all (separately carried out before) grid docking simulations OK, followed by several ns MD with Amber9 after that the complex was embedded in a lipidic membrane. For the 13-rings compound we are here trying to solve the remaining issues.


RUNS WITH 568 SPHERES:
5-rings-compound 5.7%mem usage
8-rings-compound 10.7%mem usage
13-rings-compound 27.9%mem usage

RUNS WITH 685 SPHERES
5-rings compound 8.3%mem usage
8-rings compound 15%mem usage
13-rings compound what () std.::bad_alloc

%mem usage refers to the available 23GB for the computation (NUMA-type MACHINE with 8 logical processors). Although no one of these continuous-docking runs was brought to completion, I extracted the above data when %mem usage was no more increasing.

It seems to me (correct, please, if I am wrong) % memory usage should be considered for "size" of sphere_select.sph AND "size" of the ligand.

> 
> Fourth maybe your ligand(s) do not DOCK to your receptor.
> Adding rings may produce a ligand that cannot fit into a
> pocket
> that was a previous active site.  This is research ...

YES


> 
> DOCK is only parallelized over ligands.  With one ligand in
> ligand_atom_file running in parallel is the same as running
> serially. 
> Start with serial DOCK on a small representative set of
> ligands. 
> Once you have useful serial 
> calculation then run a library of ligands in parallel.
> http://dock.compbio.ucsf.edu/DOCK_6/dock6_manual.htm#ParallelProcessing

OK, I have badly overlooked the point. I expected that there was parallelization with respect to the receptor, too. I was mislead by amber (re)scoring, where all CPUs are at work (at least as observed with the 4-CPUs previous machine, not yet tried with the 8-CPUs machine). I understand that parallelization is the hardest codification in these programs.

Thanks a lot
francesco
> 
> Scott
> 
> > --- On Mon, 4/21/08, Francesco Pietra
> <chiendarret at yahoo.com> wrote:
> > 
> > > From: Francesco Pietra
> <chiendarret at yahoo.com>
> > > Subject: Re: [Dock-fans] Fw: Re: Fw: Re: Fwd: Re:
>  Ligand Docking with DOCK6
> > > To: "Scott Brozell"
> <sbrozell at scripps.edu>
> > > Cc: "dock-fans"
> <dock-fans at docking.org>
> > > Date: Monday, April 21, 2008, 2:10 PM
> > > --- On Mon, 4/21/08, Scott Brozell
> > > <sbrozell at scripps.edu> wrote:
> > > 
> > > > From: Scott Brozell
> <sbrozell at scripps.edu>
> > > > Subject: Re: [Dock-fans] Fw: Re: Fw: Re:
> Fwd: Re: 
> > > Ligand Docking with DOCK6
> > > > To: "Francesco Pietra"
> > > <chiendarret at yahoo.com>
> > > > Cc: "dock-fans"
> > > <dock-fans at docking.org>
> > > > Date: Monday, April 21, 2008, 1:30 PM
> > > > Hi,
> > > > 
> > > > On Mon, 21 Apr 2008, Francesco Pietra wrote:
> > > > 
> > > > > Good news, I hope. Please see below. A
> quick
> > > response
> > > > would be much appreciated in order to decide
> whether
> > > to
> > > > continue or stop the calculation.  Thanks,
> francesco
> > > pietra
> > > > > 
> > > > > --- On Thu, 4/17/08, Scott Brozell
> > > > <sbrozell at scripps.edu> wrote:
> > > > > 
> > > > > > First priority is to investigate
> selected_spheres.sph.


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