RxDock: a fast, versatile, and open-source program for docking ligands to proteins and nucleic acids

RxDock is a fast and versatile open-source docking program that can be used to dock small molecules against proteins and nucleic acids. It is designed for high-throughput virtual screening (HTVS) campaigns and binding mode prediction studies.

RxDock is mainly written in C++ and accessory scripts and programs are written in C++, Perl or Python languages.

The full RxDock software package requires less than 50 MB of hard disk space and it is compilable (at this moment, only) in all Linux computers.

Thanks to its design and implementation [rDock2014], it can be installed on a computation cluster and deployed on an unlimited number of CPUs, allowing HTVS campaigns to be carried out in a matter of days.

Besides its main Docking program, the RxDock software package also provides a set of tools and scripts to facilitate preparation of the input files and post-processing and analysis of results.

About

Download

Please visit RxDock GitLab page for most up to date releases.

• Download a released version

• Get the latest code using git

Features

Fig. 1 The above image illustrates the first binding mode solution for ASTEX system 1hwi, with an RMSD of 0.88 Å.

Docking preparation

Define cavities using known binders or with user-supplied 3D coordinates. Allow -OH and -NH2 receptor side chains to rotate. Add explicit solvent molecules and structural waters. Supply pharmacophoric restraints as a bias to guide docking.

Pre-processing of input files

Define common ligand structure for performing tethered docking (requires Open Babel Python bindings). Sort, filter or split ligand files for facilitating parallelization. Find HTVS protocol for optimizing calculation time. Pre-calculate grids to decrease subsequent calculation times.

Post-processing and analysis of results

Summarize results in a tabular format. Sort, filter, merge or split results files. Calculate RMSD with a reference structure taking into account internal symmetries (requires Open Babel Python bindings).

Binding mode prediction

Predict how a ligand will bind to a given molecule. The ASTEX non-redundant test set for proteins and DOCK and RxDock test sets for RNA have been used for validating and comparing RxDock with other programs.

High-throughput virtual screening

Run for million of compounds in short time by exploiting the capabilities of computer calculation farms. Ease of parallelization in relatively unlimited CPUs to optimize HTVS running times. The DUD set has been used for validating RxDock and comparing its performance to other reference docking programs.

Fig. 2 In red mesh, definition of the cavity obtained by execution of rbcavity program.

History

The RiboDock program was developed from 1998 to 2006 by the software team at RiboTargets (subsequently Vernalis (R&D) Ltd) [RiboDock2004]. In 2006, the software was licensed to the University of York for maintenance and distribution under the name rDock.

In 2012, Vernalis and the University of York agreed to release the program as open-source software [rDock2014]. This version is developed with support from the University of Barcelona – sourceforge.net/projects/rdock.

The development of rDock stalled in 2014. Since 2019, RxTx is developing a fork of rDock under the name RxDock.

License

RxDock is licensed under GNU LGPL version 3.0.

• GNU LESSER GENERAL PUBLIC LICENSE
  • 0. Additional Definitions.
  • 1. Exception to Section 3 of the GNU GPL.
  • 2. Conveying Modified Versions.
  • 3. Object Code Incorporating Material from Library Header Files.
  • 4. Combined Works.
  • 5. Combined Libraries.
  • 6. Revised Versions of the GNU Lesser General Public License.

Contributor concordat

RxDock adheres both to No Code of Conduct and Code of Merit.

• Contributor Code of Conduct
• Code of Merit

References

If you are using RxDock in your research, please cite [rDock2014]. Former software reference provided for completeness is [RiboDock2004].

[rDock2014] (1,2,3)

Ruiz-Carmona, S., Alvarez-Garcia, D., Foloppe, N., Garmendia-Doval, A. B., Juhos S., et al. (2014) rDock: A Fast, Versatile and Open Source Program for Docking Ligands to Proteins and Nucleic Acids. PLoS Comput Biol 10(4): e1003571. doi:10.1371/journal.pcbi.1003571

[RiboDock2004] (1,2)

Morley, S. D. and Afshar, M. (2004) Validation of an empirical RNA-ligand scoring function for fast flexible docking using RiboDock®. J Comput Aided Mol Des, 18: 189–208. doi:10.1023/B:JCAM.0000035199.48747.1e

Getting started guide

In this section, you have the documentation with installation and validation instructions for first-time users.

To continue with a short validation experiment (contained in the Getting started guide), please visit the Validation experiments section.

Contents:

• Overview
• Quick and dirty installation
  • Installation in 3 steps
  • Installation tutorial
• Prerequisites
  • Compilers
  • Required packages
• Unpacking the distribution files
  • Example unpacking procedure
• Building
  • Customising the tmake template for a build target
  • Build procedure
• Validation experiments
  • Binding mode prediction in proteins
  • Binding mode prediction in RNA
  • Database enrichment (actives vs. decoys – for HTVS)

Reference guide

In this section you can find the documentation containing full explanation of all RxDock software package and features.

For installation details and first-users instructions, please visit Installation and Getting started sections.

Contents:

• Preface
• Acknowledgements
• Introduction
• Configuration
  • Input file locations
  • Launching executables
• Cavity mapping
  • Two sphere method
  • Reference ligand method
• Scoring functions
  • Component scoring functions
  • Intermolecular scoring functions under evaluation
  • Code implementation
  • References
• Docking protocol
  • Protocol summary
  • Code implementation
  • Standard RxDock docking protocol (dock.prm)
• System definition file
  • Receptor definition
  • Ligand definition
  • Solvent definition
  • Cavity mapping
  • Cavity restraint
  • Pharmacophore restraints
  • NMR restraints
  • Example system definition files
• Molecular files and atom typing
  • Atomic properties
  • Difference between formal charge and distributed formal charge
  • Parsing a MOL2 file
  • Parsing an SD file
  • Assigning distributed formal charges to the receptor
• File formats
  • .prm file format
  • Water PDB file format
  • Pharmacophore restraints file format
• Programs
  • Programs reference
• Appendix

User guide

Contents:

• Docking in 3 steps
  • Step 1: System definition
  • Step 2: Cavity generation
  • Step 3: Docking
• Docking strategies
  • Standard docking
  • Tethered scaffold docking
  • Docking with pharmacophore restraints
  • Docking with explicit waters
• Multi-step protocol for HTVS
  • Step 1: Create the multi-step protocol
  • Step 2: Run docking with the multi-step protocol
• Calculating ROC curves
  • R commands for generating ROC curves
• Running docking jobs in parallel
  • Step 1: Split molecules input file
  • Step 2: Run docking jobs with splitted files
• Pharmacophoric restraints
  • Step 1: Pharmacophoric restraints file
  • Step 2: RxDock system definition file
  • Step 3: Optional constraints

Developer guide

Contents:

• Target platforms
  • Primary and secondary target platforms
  • Tertiary and quaternary target platforms
• Build system
  • Rationale
• Coding standards
  • LLVM coding standards and additions
  • See also
• Documentation
  • General documentation
  • Codebase documentation
• Versioning
  • Version control system
  • Version numbering

Support

If you are having some trouble regarding usage, compilation, development or anything else, you can use different options to ask for support.

Mailing lists

If you are having any kind of trouble, you have any questions or anything related to general usage of the program please search and use our the discussion section of RxDock channel on Telegram.

Issue tracker

Mostly for developers and code-related problems. If you find a bug, please report it in issues section in RxDock GitLab project.