[ VLS Intro | Start | Database Format | Preferences | Docking Project Table File | Run VLS in the Graphical User Interface | Parallelization | VLS Results ]

ICM-VLS docks a compound database into a prepared receptor and evaluates the resulting poses with a binding-score function. Poses that meet the configured retention criteria are saved for subsequent analysis.

VLS uses the same receptor preparation and project setup as individual-ligand docking. Validate that setup with known ligands when available and run a small pilot screen before screening the full library.

1. Prepare the docking project and generate receptor maps.
2. Review ligand preparation and general docking preferences.
3. Prepare the database index and select the input using Docking/Setup Batch Ligand/From Indexed Database.
4. Set the screening preferences, including filters and score threshold.
5. Run a pilot screen, inspect the results, and then start the full screen or use parallel jobs.
6. Create a hitlist and use the shared analysis tools to prioritize compounds.

For the indexed-database workflow, use an SDF or MOL2 ligand file and create an ICM index. The index provides fast access to individual molecular records without loading the complete library into a table.

To index an sdf file:

• Click on the menu Docking/Tools/Index Mol/Mol2 File/Database to generate the index. The following data entry box will be displayed.

• Enter the name of your Mol/Mol2 file and enter the name you wish to call your index file.
• Select whether your file is in Mol or Mol2 format.

VLS preferences can be setup by:

• Selecting the menu Docking/Preferences/Database Scan

Different options are available to select by clicking the down arrow next to the data entry field. These options are described here:

Score Threshold:

Only poses with a score below the configured threshold are retained. Choose the threshold from known-ligand scores or a pilot screen of approximately 1000 library compounds. Retaining roughly 1 percent can be an initial target, but adjust the threshold to the receptor, library, and number of compounds you intend to review. See Scoring for interpretation.

Potential of mean force score:

Potential of mean force calculation ( pmf ) provides an independent score of the strength of ligand-receptor interaction. The pmf-parameters are stored in the icm.pmf file.

Other selection criteria:

Other selection criteria which can be changed include

Minimum/Maximum Ligand Size you wish to be screened.

Maximum number of H-bond donors

Maximum number of H-bond acceptors

Maximum number of torsions

ICM VLS uses a number of criteria to pre-select compounds before docking. Edit the project .dtb file to change their defaults. A full description of each field in the .dtb file can be found here https://molsoft.com/addons/ftp/man/dockTable.pdf

#>i DOCK1.i_maxHdonors 
5 
#>i DOCK1.i_maxLigSize 
500 
#>i DOCK1.i_maxNO 
10 
#>i DOCK1.i_maxTorsion 
10 
#>i DOCK1.i_minLigSize 
100

First setup the docking project (From Set Project to Setup Batch Ligand)

To start the vls job:

• Docking/Run Docking Batch

[ Gui Jobs | Run Jobs from the Command Line ]

In the GUI you can run the screening in parallel in the following ways.

• Setup the docking project.
• Check the docking preferences and the database scan preferences. If you are screening millions of chemicals it is usually a good idea to run a test screen of a smaller set so you can see the likely range of scores.
• Index the SDF file you wish to screen using Docking/Tools/Index Mol/Mol2 File/Database.
• Select the indexed database using Docking/Setup Batch Ligand/From Indexed Database.
• Docking/Run Docking VLS Batch and enter the number of CPU threads you wish to use on your local machine by entering the number in the Number of Parallel Jobs dialog window. For example if you have a 4 cpu machine with 2 threads each you could split your screening up into 8 parallel jobs.
• Then the docking will run. In your docking directory you will see multiple .ou file according to the number of parallel jobs you are running.

Or there is a more interactive way as described below.

• Select Docking/Run Docking VLS Batch
• Select the Local VLS Batch option.
• Select the docking project name.
• Enter the compound number you would like to dock from e.g. 8001
• Enter the compound number you would like to dock to e.g. 10000
• License type: For nearly all licenses (e.g. standard ICM-VLS licenses) types you need to leave this entry blank. If you have a -vlscluster license or a molvls license (-vls) then select the option from the drop down list. Any questions first check your license.dat file or Email support@molsoft.com.

Or if you have a queuing system installed on the machine you are running the GUI you can use the tab VLS via Queueing System and this will split the screen into the number of jobs you specify and submit the jobs.

To run vls on the command line on a server or cloud machine.

• Setup the docking project.
• Check the docking preferences and the database scan preferences. If you are screening millions of chemicals it is usually a good idea to run a test screen of a smaller set so you can see the likely range of scores.
• Index the SDF file you wish to screen using Docking/Tools/Index Mol/Mol2 File/Database.
• Select the indexed database using Docking/Setup Batch Ligand/From Indexed Database. Check that the path to the database is correct in the docking_project.dtb file - you might need to add the path in the fields shown below.

#>s dockCOX.s_dbFile
/home/molsoft/celebrex50.sdf
#>s dockCOX.s_dbIndex
/home/molsoft/celebrex50.inx

• Send the jobs using _dockScan.

Create a docking hitlist from the answer files. For parallel runs, include all relevant answer files using a matching wildcard pattern. The shared results section explains scores, alternative poses, display options, and export.

Use post-screen analysis to compare scores, interactions, and chemical diversity before selecting compounds for follow-up.