rDock Docking

CATEGORY

3D

SOURCE

Commercial Open Source

DESCRIPTION

Ligand docking using rDock

INPUTS

A Dataset of Molecules with the ligands to dock

A zip file with the docking configuration (see below)

OUTPUTS

A Dataset of Molecules with the docked poses

OPTIONS

Number of dockingsThe number of docking runs for each ligand. Each run will generate a different pose.
Top scoring posesThe number of top scoring poses to output.
Score filterOptional score above which poses are not output. The score is an approximation to the binding energy, and will typically be a negative number like -23.1 with stronger binding having LARGER negative numbers. You need to study the scores against a particular target to get an understanding of a sensible filter to use.
Normalised score filterOptional normalised score above which poses are not output. The normalised score is the score divided by the number of heavy atoms in the ligand, and takes the size of the ligand better into account.

ADDITIONAL INFO

Introduction

rDock is a molecular docking program, originally created by RiboTargets, which became Vernalis. It was open sourced in 2012. For more information on rDock look here.

Options

Key to using this cell is providing the docking configuration as a zip file. This file must contain the following:

  • receptor.mol2 - the receptor structure in mol2 format
  • receptor.prm - the rDock parameters file
  • receptor.as - the cavity definition prepared using the rdock tools e.g. the rbcavity program

A good way of doing this is the Docking Validation project that Informatics Matters has created as an upstream project for Squonk. In particular there is an example for DHFR that you can follow that can be found here.

To generate the receptor structure you may need a third party program like MOE or Maestro, but we are hoping to provide a freely usable alternative in the future. To generate the parameters file and the cavity definition file see the rDock documentation. For information about Nextflow see nextflow.io. An example zip file is attached to this page.

The zip file can be uploaded using the ZipFileUpload cell.

Performing docking

This cell uses a lot of computing power. It is currently only suitable for around 1000 dockings (inputs * number of dockings).

Docking comprises 3 key steps

  1. Preparing the docking configuration. Currently that is done outside of Squonk and the files packed up into a zip file. This is a complex process to be performed by an expert. Once done the zip file is uploaded using the ZipFileUpload cell.
  2. Preparing the ligands. At the minimum 3D structures are needed, but you might also want to perform other operations such as enumerating stereoisomers and tautomers, and adjusting the charge state. Some prototype cells for these operations exist (e.g. Molecule Enumerator cell), but more work is expected here.
  3. Performing the docking using this cell. Its inputs are the results of steps 1 and 2. The output is the docker poses. It is expected that this is a relatively non-expert step and can be done by most users.

This is a minimal example of running a docking experiment:

Typically you might view the output in the NGLViewer cell.

Future plans

We plan much more for this cell, and related cells. Some examples:

  • A cell that can provide the configuration details directly from a given PDB file
  • More control over docking options
  • Tethered docking
  • Similar cells for other docking programs