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

Scott Brozell sbrozell at scripps.edu
Thu Apr 3 14:23:35 PDT 2008


Hi,

On Wed, 2 Apr 2008, Francesco Pietra wrote:

> With Dock v. 6.2, I run serial interactive
> $ dock6 -i rigid_nogrid.in
> where the in file was added of
> cont_score_rep_rad_scale   1
> cont_score_use_dist_dep_dielectric yes
> as printed below:
> 
> ligand_atom_file /home/francesco/dockwork/ctx3c_dock62/ligand.mol2
> limit_max_ligands no
> skip_molecule   no
> read_mol_solvation no
> calculate_rmsd   no
> orient_ligand   yes
> automated_matching yes
> receptor_site_file /home/francesco/dockwork/ctx3c_dock62/selected_spheres.sph
> max_orientations  1000
> critical_points  no
> chemical_matching no
> use_ligand_spheres no
> flexible_ligand  no
> bump_filter    no
> score_molecules  yes
> contact_score_primary no
> contact_score_secondary no
> grid_score_primary   no
> grid_score_secondary  no
> grid_score_rep_rad_scale no
> grid_score_vdw_scale   no
> grid_score_es_scale   no
> grid_score_grid_prefix no
> dock3.5_score_secondary no
> continuous_score_primary yes
> continuous_score_secondary no
> cont_score_rec_filename /home/francesco/dockwork/ctx3c_dock62/protein.mol2
> cont_score_rep_rad_scale  1
> cont_score_use_dist_dep_dielectric yes
> cont_score_att_exp         6
> cont_score_rep_ex         12
> cont_score_dielectric       4.0
> cont_score_vdw_scale       1
> cont_score_es_scale       1
> gbsa_zou_score_secondary    no
> gbsa_hawkins_score_secondary  no
> amber_score_primary      no
> amber_score_secondary     no
> minimize_ligand        yes
> simplex_max_iterations    1000
> simplex_max_cycles      1
> simplex_score_converge    0.1
> simplex_cycle_converge    1.0
> simplex_trans_step      1.0
> simplex_rot_step       0.1
> simplex_tors_step      10.0
> simplex_final_min      no
> simplex_random_seed     0
> atom_model         all
> vdw_defn_file    /usr/local/dock6/parameters/vdw_AMBER_parm99.defn
> flex_defn_file       /usr/local/dock6/parameters/flex.defn
> flex_drive_file      /usr/local/dock6/parameters/flex_drive.tbl
> ligand_outfile_prefix   rigid_nogrid
> write_orientations    no
> num_scored_conformers_written 1
> rank_ligands         no
> 
> accepting defaults. A statement was also presented which was not in the in file:
> 
> num_scored_conformers  [1]

Yes num_scored_conformers replaced num_scored_conformers_written in 6.2.
It is useful to first try old inputs interactively when the DOCK version
has been updated to underscore input changes.

> I accepted the [1] default..
> 
> It run out of memory:
> 
> Initialing Library File Routines ...
> Initializing Orienting Routines...
> Error: memory exhausted!
> If this occurs during grid reading then a likely cause is a grid that is too large.
> Some machines have a very restrictive policy on allocating available resources: For
> Unix platforms increase the datasize, stacksize, and memoryuse using the limit,
> ulimit, or unlimit commands; use trial and error to find the apt one of the
> commands.
> 
> terminate called after throwing an instance of 'std::bad_alloc'
> what(): St9bad_alloc
> Aborted
> _______-
> It was not reading grid. I use Debian Linux amd64. The memory is set with shmmax and
> when computing with nwchem all 16GB available are used.
> 
> Command
> ulit
> repots
> unlimited

Huh, what is the complete output of the limit command ?
What are the sizes of your grid and sphere files; use ls -ls
Run dock6 and send the top output for that process; see below.


> I did nothing recently about "datasize" "stacksize". Should I investigate about
> these?

Definitely, isn't that clear from the error message ?
This error message seems clear to me, and I wonder why it is ignored:
http://blur.compbio.ucsf.edu/pipermail/dock-fans/2008-March/001468.html


I have confirmed that continuous score will substitute for grid score
in flexible docking.  Here are some memory highlights:

cd dock6/install/test/grid_score
../../../bin/dock6 -i grid2.dockin -o grid2.dockout
top  shows
  PID USER PR NI VIRT RES SHR S %CPU %MEM TIME+ COMMAND
 23224 srb 17 0 43464 3352 1652 R 99 0.0 0:01.35 dock6
with the verbatim dock6/install/test/grid_generation
grid_spacing                   0.5
   356 -rw-r--r-- 1 srb appl    359152 Apr  3 15:55 grid.nrg

Radically increasing the size of the grid:
  4031  sb 18 0 337m 298m 1652 R 80 3.7 0:01.18 dock6
grid_spacing                   0.05
302848 -rw-r--r-- 1          309805888 Apr  3 15:41 grid.nrg

For continuous score 
 22689 srb 25 0 44848 4808 1696 R 100 0.1 0:06.96 dock6

grid2.dockin input files diff
24c24
< grid_score_primary                                           yes
---
> grid_score_primary                                           no
26,29c26
< grid_score_rep_rad_scale                                     1
< grid_score_vdw_scale                                         1
< grid_score_es_scale                                          1
< grid_score_grid_prefix                                       ../grid_generation/grid
---
> dock3.5_score_primary                                        no
30a28
> continuous_score_primary                                     yes
31a30,37
> cont_score_rec_filename                                      rec.mol2
> cont_score_att_exp                                           6
> cont_score_rep_exp                                           12
> cont_score_rep_rad_scale                                     1
> cont_score_use_dist_dep_dielectric                           yes
> cont_score_dielectric                                        4.0
> cont_score_vdw_scale                                         1
> cont_score_es_scale                                          1

Scott

> --- On Mon, 3/31/08, Scott Brozell <sbrozell at scripps.edu> wrote:
>       From: Scott Brozell <sbrozell at scripps.edu>
>       Subject: Re: Fwd: Re: [Dock-fans] Ligand Docking with DOCK6
>       To: "Francesco Pietra" <chiendarret at yahoo.com>
>       Cc: "dock-fans" <dock-fans at docking.org>
>       Date: Monday, March 31, 2008, 4:11 PM
> 
> Hi,
> On Sat, 22 Mar 2008, Francesco Pietra wrote:
> > While waiting for a clarification about the manual indication for
> continuous
> > score "Regardless of the exponent used, the same radii and
> well-depths are
> > used", I have tried a rigid docking on the same system (protein and
> large
> > ligand) by neglecting the information on radius 25A for the sphere used
> for
> > building the grid.
> see
> http://blur.compbio.ucsf.edu/pipermail/dock-fans/2008-March/001489.html
> > mpirun -np 4 dock6.mpi -i rigid_nogrid.in -o rigid_nogrid.out
> > 
> > again led to segmentation fault, though less rapidly than when using grid.
> In
> > the few seconds inter lapsed, I had the opportunity to look at "top
> -i: the
> > memory used was 0.1% on all
>  four processors (each used 100%).
> > 
> > Input rigid_nogrid.in:
> > 
> > ligand_atom_file /home/francesco/dockwork/ligand.mol2
> > limit_max_ligands                                            no
> > skip_molecule                                                no
> > read_mol_solvation                                           no
> > calculate_rmsd                                               no
> > orient_ligand                                                yes
> > automated_matching                                           yes
> > receptor_site_file /home/francesco/dockwork/selected_spheres.sph
> > max_orientations                                             1000
> > critical_points                                              no
> > chemical_matching                                            no
> > use_ligand_spheres                                           no
> > flexible_ligand  
>                                             no
> > bump_filter                                                  no
> > score_molecules                                              yes
> > contact_score_primary                                        no
> > contact_score_secondary                                      no
> > grid_score_primary                                           no
> > grid_score_secondary                                         no
> > grid_score_rep_rad_scale                                     no
> > grid_score_vdw_scale                                         no
> > grid_score_es_scale                                          no
> > grid_score_grid_prefix                                       no
> > dock3.5_score_secondary                                      no
> > continuous_score_primary                                     yes
> > continuous_score_secondary                     
>               no
> > cont_score_rec_filename  /home/francesco/dockwork/protein.mol2
> > cont_score_att_exp                                           6
> > cont_score_rep_ex                                           12
> > cont_score_dielectric                                        4.0
> > cont_score_vdw_scale                                         1
> > cont_score_es_scale                                          1
> > gbsa_zou_score_secondary                                     no
> > gbsa_hawkins_score_secondary                                 no
> > amber_score_primary                                          no
> > amber_score_secondary                                        no
> > minimize_ligand                                              yes
> > simplex_max_iterations                                       1000
> > simplex_max_cycles                                           1
> >
>  simplex_score_converge                                       0.1
> > simplex_cycle_converge                                       1.0
> > simplex_trans_step                                           1.0
> > simplex_rot_step                                             0.1
> > simplex_tors_step                                            10.0
> > simplex_final_min                                            no
> > simplex_random_seed                                          0
> > atom_model                                                   all
> > vdw_defn_file    /usr/local/dock6/parameters/vdw_AMBER_parm99.defn
> > flex_defn_file               /usr/local/dock6/parameters/flex.defn
> > flex_drive_file           /usr/local/dock6/parameters/flex_drive.tbl
> > ligand_outfile_prefix                                 rigid_nogrid
> > write_orientations                                           no
> >
>  num_scored_conformers_written                                1
> > rank_ligands                                                 no
> This file is still missing e.g.,
> cont_score_rep_rad_scale
> so verify the final input file; (note dock may write to the input file).
> I'd make the first run a serial interactive one.
> > The screen output was the same as on the failed rigid dock using grid:
> This could mean that your active site representation is the culprit.
> Scott
> > Initializing MPI Routines...
> > Initializing MPI Routines...
> > Initializing MPI Routines...
> > Initializing MPI Routines...
> > terminate called after throwing an instance of 'std::bad_alloc'
> >   what():  St9bad_alloc
> > [deb64:03626] *** Process received signal ***
> > [deb64:03626] Signal: Aborted (6)
> > [deb64:03626] Signal code:  (-6)
> > [deb64:03626] [ 0] /lib/libpthread.so.0
>  [0x2b1d13ba0410]
> > [deb64:03626] [ 1] /lib/libc.so.6(gsignal+0x3b) [0x2b1d13cd807b]
> > [deb64:03626] [ 2] /lib/libc.so.6(abort+0x10e) [0x2b1d13cd984e]
> > [deb64:03626] [ 3]
> >
> /usr/lib/libstdc++.so.6(_ZN9__gnu_cxx27__verbose_terminate_handlerEv+0x114)
> > [0x2b1d13843424]
> > [deb64:03626] [ 4] /usr/lib/libstdc++.so.6 [0x2b1d138415a6]
> > [deb64:03626] [ 5] /usr/lib/libstdc++.so.6 [0x2b1d138415d3]
> > [deb64:03626] [ 6] /usr/lib/libstdc++.so.6 [0x2b1d138416ba]
> > [deb64:03626] [ 7] dock6.mpi [0x42c654]
> > [deb64:03626] [ 8] /usr/lib/libstdc++.so.6(_Znwm+0x34) [0x2b1d13841954]
> > [deb64:03626] [ 9] /usr/lib/libstdc++.so.6(_Znam+0x9) [0x2b1d13841a49]
> > [deb64:03626] [10] dock6.mpi(_ZN6Orient12match_ligandER7DOCKMol+0x33d)
> > [0x44b9bd]
> > [deb64:03626] [11] dock6.mpi(main+0x90a) [0x42cf6a]
> > [deb64:03626] [12] /lib/libc.so.6(__libc_start_main+0xda) [0x2b1d13cc54ca]
> >
>  [deb64:03626] [13] dock6.mpi(__gxx_personality_v0+0xba) [0x41bf9a]
> > [deb64:03626] *** End of error message ***
> > mpirun noticed that job rank 0 with PID 3625 on node deb64 exited on
> signal 15
> > (Terminated). 
> > 3 additional processes aborted (not shown).
> > 
> > 
> > Should this attempt not follow what you had in mind, please suggest me
> what to
> > modify and I'll do again.
> > Thanks
> > francesco
> > 
> > 
> > 
> > --- Scott Brozell <sbrozell at scripps.edu> wrote:
> > 
> > > Hi,
> > > 
> > > Ok, thanks for the updated report; we are keeping memory tuning
> > > on our todo list.
> > > 
> > > Here is an idea off the top of my head: try 
> > > grid_score_primary no
> > > continuous_score_primary yes
> > > This may trade cputime for memory.
> > > Study the manual to keep the dock and grid settings
>  consistent:
> > > http://dock.compbio.ucsf.edu/DOCK_6/dock6_manual.htm#ContinuousScore
> > > 
> > > If this works then there are definitely some easy cputime tunings
> > > for continuous_score.




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