Building The 3D Pipeline ZINC22
Introduction
The 3D pipeline is a collection of scripts and software packages that enable the massively parallel creation of dockable 3D molecules.
EZ Setup
BKS Cluster
source /nfs/soft/dock/versions/dock38/pipeline_3D_ligands/env.(sh|csh)
This environment will set up most of the required variables for you, as well as adds the submission scripts to your PATH, which means submission can be as simple as:
bash
export INPUT_FILE=$HOME/myligands.smi export OUTPUT_DEST=$HOME/myoutput submit-all-jobs-slurm.bash
csh
setenv INPUT_FILE $HOME/myligands.smi setenv OUTPUT_DEST $HOME/myoutput submit-all-jobs-slurm.bash
Wynton Cluster
source /wynton/group/bks/soft/pipeline_3D_ligands/env.(sh|csh)
Similar to the BKS example, this environment will set most of the required variables for you
bash
export INPUT_FILE=$HOME/myligands.smi export OUTPUT_DEST=$HOME/myoutput submit-all-jobs-sge.bash
csh
setenv INPUT_FILE $HOME/myligands.smi setenv OUTPUT_DEST $HOME/myoutput submit-all-jobs-sge.bash
Script Arguments
Main submission scripts are named submit-all-jobs-slurm.bash and submit-all-jobs-sge.bash. These scripts use environment variables as arguments instead of usual command line ones.
E.g, on bash you would pass one of these arguments like so:
export INPUT_FILE=$PWD/example.smi
or on csh:
setenv INPUT_FILE $PWD/example.smi
Prior to running the script.
Repackaging Output For Docking
The output of the 3D pipeline scripts will be a number of tar.gz files with roughly LINES_PER_JOB molecules contained per package.
It is standard practice to repackage these smaller packages into larger packages for docking, as 50 molecules do not take long to process with DOCK.
See this wiki page for how to do this: Repackaging_DB2_DOCK38
Required Arguments
INPUT_FILE
The input .smi file to be built. This file should contain only two columns of data: (SMILES, NAME) with no header.
OUTPUT_DEST
The base directory for output to be stored. The script will create a sub-directory here named $INPUT_FILE.batch-3d.d
Within this output directory there are 3 sub-directories:
- in
- log
- out
In contains the input file split into fragments and sub-fragments. By default the script first splits the input file into batches of 50000, then splits those batches into sub-batches of 50. Each individual job works on one of these sub-batches. Each array batch job works on one of the batches of 50000. All of the other directories alongside 'in' share the same directory structure.
Log contains log messages from the jobs. If you are re-submitting a file, be aware that log messages from previous runs on this file will be overwritten.
Out contains tar.gz output from each job. The tarballs should contain a number of 3d molecule formats for each molecule in the batch, including 1 or more db2.gz files.
SOFT_HOME
Where software tarballs for the pipeline are stored. Symbolic links should be maintained in this directory according to the rules described in the "software arguments" section of this page. If you're sourcing a premade environment, don't worry about setting this value.
LICENSE_HOME
Where software licenses are stored. Currently our licensed software includes jchem and openeye, licenses must be named .jchem-license.cxl and .oe-license.txt respectively. if you're sourcing a premade environment, don't worry about setting this value.
Script Arguments
SHRTCACHE
The base working directory for the script. By default it is /scratch
LONGCACHE
The base directory for persistent files that are shared between jobs to go (i.e where software is installed). By default it is /scratch.
CORINA_MAX_CONFS
How many nitrogen flapping configurations of each protomer corina should generate. By default only one is generated.
Omega Arguments
These parameters correspond to torsion driving parameters described in the omega manual: https://docs.eyesopen.com/applications/omega/omega/omega_opt_params.html#torsion-driving-parameters
If you'd like to know more about how these parameters function, cross reference with the manual page.
OMEGA_MAX_CONFS
Maximum configurations OMEGA will generate, default 600.
OMEGA_ENERGY_WINDOW
Torsion energy window, if set to zero OMEGA will use an alternative rotatable bond dependent window method instead. Default is 12
OMEGA_TORLIB
Torsion library- can choose between GubaV21 or Original, default is Original.
OMEGA_FF
Default is MMFF94Smod.
OMEGA_RMSD
Sets rmsd for clustering and filtering conformations. If zero, omega will use an alternative rotatable-bond dependent method instead. Default is 0.5
Job Submission Arguments
SUBMIT_MODE
Choose the job submission method, choose between SGE, SLURM, or TEST_LOCAL. This will be automatically set if you use the job controller's corresponding superscript, e.g submit-all-jobs-slurm.bash. TEST_LOCAL will bypass the job controller and run the first input chunk in your shell.
LINES_PER_BATCH
How many lines of the source .smi file should be processed per array batch job, default is 50000.
LINES_PER_JOB
How many lines of the batch .smi file should be processed per array task, default is 50.
MAX_BATCHES
Each batch job will contain LINES_PER_BATCH/LINES_PER_JOB jobs, and there will be a maximum of MAX_BATCHES batches submitted at any given time. By default this value is 25, which corresponds to 25,000 queued jobs at any given time if there are 1000 jobs per batch.
The submit-all script will block until less than MAX_BATCHES job arrays are in the queue. TODO: block until less than MAX_BATCHES total jobs are running or in the queue.
SBATCH_ARGS
Additional arguments for the sbatch command. It is recommended to set a --time limit, as build jobs will save progress & terminate if they are still running two minutes before the --time limit.
QSUB_ARGS
Additional arguments for the qsub command. Similar to slurm, it is recommended to set a time limit, but you will need to manually specify both s_rt & h_rt. In the example, we set s_rt to be a minute and thirty seconds before h_rt. s_rt is the point where jobs will save progress and terminate, h_rt is when they will be forcibly terminated, even if they've not finished saving.
Software Options
All software variables will be set automatically if there exists a symbolic link in $SOFT_HOME matching the software variable's name, for example:
dock-latest -> DOCK.3.8.4.3d.tar.gz jchem-latest -> jchem-19.15_r1.tar.gz pyenv-latest -> lig_build_py3-3.7.1.tar.gz
They may also bet set manually- value is expected to be a path to a tar.gz file.
We use the following software:
- DOCK_VERSION
- JCHEM_VERSION
- PYENV_VERSION
- CORINA_VERSION
- OPENBABEL_VERSION
- EXTRALIBS_VERSION
- JAVA_VERSION
Examples
Minimal Example
export INPUT_FILE=$PWD/example.smi export OUTPUT_DEST=$PWD bash submit-all-jobs-slurm.bash
BKS Example - limit time to 2 hours, change batch size variables. Slurm tasks should automatically save progress when reaching their time limit.
export INPUT_FILE=$PWD/example.smi export OUTPUT_DEST=$PWD/ligand_building export SBATCH_ARGS="--time=02:00:00" export LINES_PER_BATCH=20000 export LINES_PER_JOB=25 export MAX_BATCHES=15 bash submit-all-jobs-slurm.bash
Wynton Example - limit time to 30 minutes, but set a soft limit 1:30 prior to the hard limit - the interrupt generated by the soft limit will signal the job to save progress for any resubmissions and exit.
export INPUT_FILE=$PWD/example.smi export OUTPUT_DEST=$PWD/ligand_building export QSUB_ARGS="-l s_rt=00:28:30 -l h_rt=00:30:00 -r y" bash submit-all-jobs-sge.bash
Resubmission
If your jobs for building have finished (or timed out), and you want to continue process whatever has not been processed yet, just run submit-all-jobs-slurm/sge again (with same env arguments). The submit-all script will detect which entries haven't finished and resubmit them.
Repatriation
At BKS, we currently store the tarred output of the pipeline @ /nfs/exb/zinc22/tarballs. Currently, we use the following command to repatriate output from other clusters to our cluster:
### migrate_output.bash
for output in $OUTPUT_DEST/*.batch-3d.d; do
echo "starting rsync on $output to $MIGRATE_USER@files2.docking.org"
sshpass -f $PW_FILE rsync -arv $output/out $MIGRATE_USER@files2.docking.org:/nfs/exb/zinc22/tarballs/$(basename $output).out
done
sshpass is optional here but preferable for convenience's sake. Since files2.docking.org is only visible within the UCSF network, any clusters outside will need to maintain a network tunnel when rsyncing.
Errors
Sometimes an output tarball will have few or no entries within. Certain molecule types will fail to be built, and often these molecules get bunched together (i.e if the input file is sorted by SMILES). Additionally, a small percentage of all molecules may fail to be processed by corina or amsol. If neither of these explain what is causing your missing entries, check that tarball's corresponding log entry for more info.
Additional Notes
It is safe to re-run the same file multiple times- the script takes care of making sure not to re-run any jobs that have already completed successfully prior. This is only the case if that file's corresponding batch-3d.d output directory has not been moved or deleted.
For example, if one of your nodes went down and caused a bunch of jobs to fail, it would be safe to re-run ./submit-all-jobs.bash to re-submit those jobs. (assuming there are no jobs for that file currently queued/running)
back to ZINC22:Building_3D