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

Francesco Pietra chiendarret at yahoo.com
Tue Apr 22 01:38:53 PDT 2008


Hi:
As anticipated below, I have killed the serial procedure because (after 2526 min CPU time; nearly two full days wall time), the "top -i" and *.out file remained the same as after 100 min CPU time (situation reported below) and there was no way to check if the procedure was advancing or not.

Now I have launched the same flex docking, continuous score in parallel (8 logical CPUs) with same *.in file and adding -v for verbosity.

The *.out file started with 8 lines:

Initializing MPI Routines ...

and ends with

Initializing Library File Routines..
Initializing Orienting Routines ..
Initializing Conformer Generator Routines...
VERBOSE MOLECULE STATS
Number of heavy atoms 3417
Number of rotatable bonds 2120

There are also *.out.# (# from 1 to 5) files.

*.out.1 shows for verbosity:
Number of heavy atoms 73
Number of rotatable bonds 3.

*.out.2 and *.out.3. *.out.4 and *.out. show:
Number of heavy atoms 3417
Number of rotatable bonds 2120.
Dock is currently running on deb64
0 Molecule Processed.



"top -i"

Initially showed 8 lines, 7 for the CPUs. Rapidly the active CPUs are only two (rarely a third one appears with zeo %CPU and %MEM)

PID (3736), USER (f), PR (25), NI (0), VIRT
(7051m), RES (6.5g), SHR (4192), S (R), %CPU (100), %MEM
(28.2), TIME+ (12), COMMAND (dock6.mpi).

PID (3735), USER (f), PR (25), NI (0), VIRT
(370m), RES (11m), SHR (4176), S (R), %CPU (100), %MEM
(0), TIME+ (12), COMMAND (dock6.mpi).

The two sets of data exchange frequently the PID number. The %MEM and RES are increasing, reaching at TIME+ 50 the values observed before for the serial run.
______________

I offer a comment of the sphere_select.sph size. It has little meaning alone. With a 106-atoms ligand, the largest selected_spheres.sph (10,536,750 points) is dealt with fine in grid scoring with box 12A. Under the same conditions, increasing the size of the ligand to 118 atoms, crash occurs as described. I must add that these are ring-fused compounds, so that the increased number of atoms pertains to rings which (as far as I understand) are treated as rigid bodies. So, this appears to me a curious trend. I have also to add that reducing the selected_spheres.sph to 7,675,200, in a 8A box, does not provide room enough to the ligand in grid scoring, although the spheres still cover most of the protein. Therefore, I do not understand your suggestion "If you are uneasy then try a much smaller calculation for verification and benchmarking." I am not uneasy, I am used at the problems of scientific research, though I can't imagine how to check the issues with a
 smaller calculations: the largest sphere_select.sph is OK for a slightly smaller ligand.

It seems to me that there is little hope with present parallel procedure. It seems to go on as a serial run. Actually, the two-CPUs issue is what was regularly observed in the past, even for successful runs. I saw all CPU at work only for amber score. Though, I understand these are complex affairs. I can't rule out to be missing some obvious point, and hope my posting is not disturbing developers an audience. Is any hope that present parallel procedure may give some hint? Wait for your advice before killing it.

Thanks
francesco pietra





--- 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.
> > > > 
> > > > Scott
> > > 
> > > With my new machine (NUMA-type 4 dual-opteron 875
> for
> > a total 8 logical CPUs, 23GB mem + 1GB for debian
> linux
> > amd6a) I am carrying out a flex docking on the same
> large
> > ligand where (with previous machine, 2 dual-opteron,
> 15GB
> > available mem) memory exhausion occurred both on grid
> and
> > continuous score (selected_spheres.sph was derived
> from a
> > radius 25A - comprising 10,536,750 grid points, in a
> 37088
> > b file. In all cases (also below) stack size
> unlimited.
> > > 
> > > Now, setting a 23A radius, selected_spheres
> totals
> > 7,675,200 points in a 30770 bytes file. A flex docking
> > (serial, see below the same *.in file for the above
> > unsuccessful runs) is going on. Top (dock6 command)
> showed
> > %CPU starting at 0, then rapidly 25, then 100. %Mem
> started
> > at 0, the, in 10 min 28%, reaching 29.4% (i.e.,
> 7474212
> > used). The situation is now:
> > > 
> > > PID (3744), USER (f), PR (25), NI (0), VIRT
> (7112m),
> > RES (6.8g), SHR (1624), S (R), %CPU (100), %MEM
> (29.4),
> > TIME+ (1624), COMMAND (dock6).
> > > 
> > > Nothing is being further written  to either the
> *.out
> > file or the *.mol2 file. The latter is zero bytes, the
> > former 6668 b, staying at what was initially written;
> end
> > lines read:
> > > 
> > > Initialing Library File Routines ...
> > > Initializing Orienting Routines ...
> > > Initializing Conformer Generator Routines...
> > > 
> > > *.in file:
> > > 
> > > ligand_atom_file                                 
>     
> >      
> /home/francesco/dockwork/ctx3c_flex_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_flex_dock62/selected_spheres.sph
> > > max_orientations                                 
>     
> >       1000
> > > critical_points                                  
>     
> >       no
> > > chemical_matching                                
>     
> >       no
> > > use_ligand_spheres                               
>     
> >       no
> > > flexible_ligand                                  
>     
> >       yes
> > > min_anchor_size                                  
>     
> >       40
> > > pruning_use_clustering                           
>     
> >       yes
> > > pruning_max_orients                              
>     
> >       100
> > > pruning_clustering_cutoff                        
>     
> >       100
> > > use_internal_energy                              
>     
> >       yes
> > > internal_energy_att_exp                          
>     
> >       6
> > > internal_energy_rep_exp                          
>     
> >       12
> > > internal_energy_dielectric                       
>     
> >       4.0
> > > use_clash_overlap                                
>     
> >       no
> > > bump_filter                                      
>     
> >       no
> > > score_molecules                                  
>     
> >       yes
> > > contact_score_primary                            
>     
> >       no
> > > contact_score_secondary                          
>     
> >       no
> > > grid_score_primary                               
>     
> >       no
> > > grid_score_secondary                             
>     
> >       no
> > > dock3.5_score_primary                            
>     
> >       no
> > > dock3.5_score_secondary                          
>     
> >       no
> > > continuous_score_primary                         
>     
> >       yes
> > > continuous_score_secondary                       
>     
> >       no
> > > cont_score_rec_filename                          
>     
> >      
> >
> /home/francesco/dockwork/ctx3c_flex_dock62/protein.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
> > > gbsa_zou_score_secondary                         
>     
> >       no
> > > gbsa_hawkins_score_secondary                     
>     
> >       no
> > > amber_score_secondary                            
>     
> >       no
> > > minimize_ligand                                  
>     
> >       yes
> > > minimize_anchor                                  
>     
> >       yes
> > > minimize_flexible_growth                         
>     
> >       yes
> > > use_advanced_simplex_parameters                  
>     
> >       no
> > > 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_anchor_max_iterations                    
>     
> >       500
> > > simplex_grow_max_iterations                      
>     
> >       500
> > > 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                            
>     
> >       flex
> > > write_orientations                               
>     
> >       no
> > > num_scored_conformers                            
>     
> >       1
> > > rank_ligands                                     
>     
> >       no
> > > _____________________-
> > > 
> > > Should the computation be completed? It would be
> no
> > time loss as I am interested to go on with this
> ligand,
> > though I am worried by not having any indications
> about the
> > trend of energy. Apparently there is access to disk:
> is any
> > temp file written?
> > > 
> > 
> > Probably.  It looks like selected_spheres.sph was too
> big:
> > 23A gives 7,675,200 points and yields about 7GB memory
> > consumption.
> > 25A gives 10,536,750 points and yields more than
> 15/2GB
> 
> 
> Actually more than 23G I tried on the new machine too.
> 
> > memory consumption.
> > There are no temporary files.
> > If you are uneasy then try a much smaller calculation
> for
> > verification
> > and benchmarking.
> > 
> 
> 
> Leave running overnight present job (now the top indication
> is as above, except for TIME+ 2096. Tomorrow, if still
> running without writing anything else to the *.out file,
> i.e., without any indication where the calculation is,
> I'll kill the job and retry in parallel.
> 
> As to grid scoring, spheres.sph 23A 7,675,200 points
> (corresponding to box 8A), provided no room enough for the
> ligand, according to message of failure of the flex run.
> 
> Thanks
> francesco
> > Scott
> 
> 
>      
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