[Dock-fans] Fwd: grid size (former "parameters" and "very large receptors")

Trent E. Balius tbalius at aol.com
Sun Jan 23 11:06:13 PST 2011


Your paths seem long.  Try making symbolic links and rerunning after replacing the long path name with the link.
    
ln -s /home/francesco/work_mod21/mod21_reduce/spheres/whole.r/selected_spheres.sph ./spheres.sph
    
receptor_site_file    spheres.sph
   
Hope this helps,

 
 

Trent 

 

-----Original Message-----
From: Francesco Pietra <chiendarret at gmail.com>
To: Trent E. Balius <tbalius at aol.com>
Sent: Sun, Jan 23, 2011 4:55 am
Subject: Re: [Dock-fans] Fwd: grid size (former "parameters" and "very large receptors")


I have now carried out a number of runs for one of previous  large

ligands with rigid.in instead of anchor_and_grow.in. As I still have

several different installations of dock6, compiled GNU/ACML or

intel/MKL, I tried also these. In all cases segmentation fault. With a

shared-mem machine equipped with 8GB RAM, that occurred (top -i) at

%85 RAM usage. With a shared-mem machine equipped with 24GB RAM,

segmentation fault occurred at ca 20% RAM usage. Thus, at least in the

latter case it does not seem to a be a memory problem, although the

larger the ligand, the more mem needed (I was also aware from my old

work of that requirement).



I also tried dock6.mpi on the latter machine with 8 processors. As

expected, it used all RAM and SWAP and ORTED killed the processes.



I had not used for a long time DOCK, so I was surprised that on the

current installation command "dock6 -i file.in" elicits :initializing

MPI routines ...", albeit for only one process. This is why I tried

also dock6.mpi, which initializes MPI routines for all 8 processor. On

previous compilations of dock6 (probably older versions of dock),

command "dock6 -i file.in" does not elicit any "Initializing MPI

routines. I concluded that there is nothing wrong with present

installation of dock6.4, although I did not repeat out standard tests

(also because such tests were successful at installation and now, with

a smaller ligand, anchor_and_grow was completed without errors).



Below, I have listed the rigid.in and anchor_and_grow.in files used in

my trials. Do you see anything wrong, or something that could be

modified to alleviate the process?



RIGID



ligand_atom_file

/home/francesco/work_small-ligands.all/rigid.grid.0.6.whole_39.A.CB.75/AYN.r/AYN.r.mol2

limit_max_ligands                                            no

skip_molecule                                                no

read_mol_solvation                                           no

calculate_rmsd                                               no

use_database_filter                                          no

orient_ligand                                                yes

automated_matching                                           yes

receptor_site_file

/home/francesco/work_mod21/mod21_reduce/spheres/whole.r/selected_spheres.sph

max_orientations                                             1000

critical_points                                              no

chemical_matching                                            no

use_ligand_spheres                                           no

use_internal_energy                                          yes

internal_energy_rep_exp                                      12

flexible_ligand                                              no

bump_filter                                                  no

score_molecules                                              yes

contact_score_primary                                        no

contact_score_secondary                                      no

grid_score_primary                                           yes

grid_score_secondary                                         no

grid_score_rep_rad_scale                                     1

grid_score_vdw_scale                                         1

grid_score_es_scale                                          1

grid_score_grid_prefix

/home/francesco/work_mod21/mod21_reduce/grid_box.whole.r.0.6/grid

dock3.5_score_secondary                                      no

continuous_score_secondary                                   no

gbsa_zou_score_secondary                                     no

gbsa_hawkins_score_secondary                                 no

amber_score_secondary                                        no

minimize_ligand                                              yes

simplex_max_iterations                                       1000

simplex_tors_premin_iterations                               0

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_random_seed                                          0

simplex_restraint_min                                        no

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

write_orientations                                           no

num_scored_conformers                                        1

rank_ligands                                                 no

*************************************

ANCHOR_AND_GROW



ligand_atom_file

/home/francesco/work_small-ligands.all/flex.grid.0.6.whole_39.A.CB.75/AYN.r/AYN.r.mol2

limit_max_ligands                                            no

skip_molecule                                                no

read_mol_solvation                                           no

calculate_rmsd                                               no

use_database_filter                                          no

orient_ligand                                                yes

automated_matching                                           yes

receptor_site_file

/home/francesco/work_mod21/mod21_reduce/spheres/whole.r/selected_spheres.sph

max_orientations                                             1000

critical_points                                              no

chemical_matching                                            no

use_ligand_spheres                                           no

use_internal_energy                                          yes

internal_energy_rep_exp                                      12

flexible_ligand                                              yes

min_anchor_size                                              40

pruning_use_clustering                                       yes

pruning_max_orients                                          100

pruning_clustering_cutoff                                    100

pruning_conformer_score_cutoff                               25.0

use_clash_overlap                                            no

write_growth_tree                                            no

bump_filter                                                  no

score_molecules                                              yes

contact_score_primary                                        no

contact_score_secondary                                      no

grid_score_primary                                           yes

grid_score_secondary                                         no

grid_score_rep_rad_scale                                     1

grid_score_vdw_scale                                         1

grid_score_es_scale                                          1

grid_score_grid_prefix

/home/francesco/work_mod21/mod21_reduce/grid_box.whole.r.0.6/grid

dock3.5_score_secondary                                      no

continuous_score_secondary                                   no

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_grow_tors_premin_iterations                          0

simplex_random_seed                                          0

simplex_restraint_min                                        no

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                                                 yes

max_ranked_ligands                                           500

**********************



thanks a lot

francesco





On Sat, Jan 22, 2011 at 8:50 PM, Trent E. Balius <tbalius at aol.com> wrote:

>

> I have an incomplete understanding of the orient code.  I believe the way

> that the anchor placement and sphere matching works is that the dock matches

> say 3 atoms of your ligand with 3 spheres and minimizes the residuals.  The

> code is fairly complicated and there is clustering and pruning going on.

> Perhaps others can common on this.

>

> The fact that you are getting  a segmentation fault and not just could not

> complete growth is worrisome.  If you can send me your files I can see if I

> can replicate this error.

>

> I have observed a case were the anchor was placed  with 3 spheres and was

> not well overlapped with any because of the sparse spheres.   however this

> is not common, usually one atom is placed on top of one sphere.  My earlier

> comment  might occur if you had one sphere per pocket.

>

> The code should be able to perform blind docking.  In fact it maybe better

> than audodock since dock performs incremental growth while audodock uses a

> genetic algorithm.  however this claim is untested.

>

> Trent E. Balius

> Graduate Student, Rizzo Group,

> Department of Applied Mathematics and Statistics,

> Stony Brook University.

> Office: Math Tower 3-129, Phone: (631) 632-8519

> URL: http://www.ams.sunysb.edu/~tbalius/

>

>

> -----Original Message-----

> From: Francesco Pietra <chiendarret at gmail.com>

> To: Trent E. Balius <tbalius at aol.com>

> Cc: dock-fans <dock-fans at docking.org>

> Sent: Sat, Jan 22, 2011 9:34 am

> Subject: Re: [Dock-fans] Fwd: grid size (former "parameters" and "very large

> receptors")

>

> Thanks a lot for the time you spent answering me. That we examine

>

>

> everything graphically, sphere included, is our standard routine, in

>

>

> particular the various sphere clusters I alluded to. My post was to

>

>

> show how things run (or not run) and the very reason for posting was

>

>

> the last sentence:

>

>

>

>

>

> ""Finally, why "When you have spheres in multiple pockets dock may try

>

>

> and orient the ligand to spheres located in different pockets causing

>

>

> the ligand to be placed in a vary unfavorable position and pruned

>

>

> leaving you with no orients"? Is that still inadequacy of the code

>

>

> (something that could be fixed) or that is a more serious issue?""

>

>

>

>

>

> which perhaps escaped attention. What I would aim to know is whether

>

>

> these are limitations (I have just transcribed limitations that you

>

>

> pointed out before, using just your words) by the code, limitations

>

>

> that could be fixed, or what I would like to do is beyond the

>

>

> capability of the code.

>

>

>

>

>

> I have now checked the autodck4 has no such limitations, although its

>

>

> use of partial charges and grid space pose other problems.

>

>

>

>

>

> thanks

>

>

> francesco pietra

>

>

>

>

>

> On Sat, Jan 22, 2011 at 2:30 PM, Trent E. Balius <tbalius at aol.com> wrote:

>

>

>> See manual for discussion of the spheres:

>

>

>>

>

>

>> http://dock.compbio.ucsf.edu/DOCK_6/dock6_manual.htm#SphgenOverview

>

>

>> http://dock.compbio.ucsf.edu/DOCK_6/dock6_manual.htm#SphgenOutput

>

>

>>

>

>

>> Here is an excerpt from the SphgenOverview section:

>

>

>>

>

>

>> "These sets, or clusters, are sorted according to numbers of constituent

>

>

>> spheres, and written out in order of descending size. The largest cluster

>> is

>

>

>> typically the ligand binding site of the receptor molecule. The program

>

>

>> showsphere writes out sphere center coordinates in PDB format and may be

>

>

>> helpful for visualizing the clusters (see showsphere)."

>

>

>>

>

>

>> Here is an excerpt from the discussion in the SphgenOutput section of the

>

>

>> manual

>

>

>>

>

>

>> "

>

>

>> The clusters are listed in numerical order from largest cluster found to

>> the

>

>

>> smallest. At the end of the clusters is cluster number 0. This is not an

>

>

>> actual sphere cluster, but a list of allof the spheres generated whose

>> radii

>

>

>> were larger than the minimum radius, before the filtering heuristics (

>> i.e.,

>

>

>> allowing only one sphere per atom and using a maximum radius cutoff) and

>

>

>> clustering were performed. Cluster 0 may be useful as a starting point for

>

>

>> users who want to explore a wider range of possible clusters than is

>

>

>> provided by the standard sphgen clustering routine.

>

>

>> "

>

>

>>

>

>

>> When things start not working it is always a good idea to visualize

>

>

>> everything with a molecular viewing program like Chimera.

>

>

>>

>

>

>> Cluster 0 should cover the whole receptor. Other clusters should be

>> specific

>

>

>> to a pocket as defined by the spacial clustering of the spheres.

>

>

>>

>

>

>> I strongly encourage you to visualize the clusters on your protein with

>

>

>> chimera or your favorite program to see the differences. Show the grid box

>

>

>> as well.

>

>

>>

>

>

>> Segmentation faults are always extremely frustrating.

>

>

>>

>

>

>> I am not an expert on amberscore, but I am not sure why you can't compare

>

>

>> things docked to multipule sphere sets as long as you use the same

>

>

>> receptor/grid.

>

>

>>

>

>

>>

>

>

>> Good luck and I hope this helps,

>

>

>>

>

>

>> Trent

>

>

>>

>

>

>


 
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