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Documentation for the rDock Platform

Here you can find current documentation available for the rDock platform.

Getting Started Guide [HTML]

This introductory guide is aimed at new users of rDock. It describes the minimal set of steps required to build rDock from the source code distribution, and to run one of the automated validation experiments provided in the test suite distribution.
If you only wish to use the pre-compiled version rather than building it from the source code, see tutorial 1 for a briefer setup guide.
The instructions assume that you are comfortable with simple Linux command line administration tasks, and with building Linux applications from 'make' files. Once you are familiar with these steps you should proceed to the User and Reference Guide for more detailed documentation on the usage of rDock.

Reference Guide [HTML]

This document aims to build upon the tasks covered in the Getting Started guide and be a full reference guide for the rDock platform. Whilst still in its development state at present it will eventually cover the software tools, parameter files, scoring functions and search engines. Whilst this document is being expanded the user is encouraged to cross-reference the descriptions with the corresponding source code files to discover the finer implementation details.

Science & Theory

Here you can find a brief explanation of some of the theory behind rDock.

There are three uses of this type of program:

1. Docking: Predicting the binding mode for a compound that is known to bind to a protein active site. For this, a series of different test sets of data have been assembled by the community - the Astex CCDC set is one; the rDock test set another (this includes RNA complexes). The success of docking programs is then assessed as the percentage of test complexes for which the docking program can reproduce within 2A RMSD, the crystallographically observed binding mode.

2. Virtual screening: Using docking calculations to screen a large database of compounds for those that may bind to the active site. The ability of docking programs to do this is measured by something called enrichment factors. Typically, a random set of "drug-like" molecules is assembled, spiked with compounds that are known to bind. The docking program is then used to produce a rank-ordered list of the compounds, predicting which is the most likely to bind. The enrichment factor is then calculated as the ratio of the number of known compounds found in the top (say) 5% of ranked compounds compared to that expected by random. This is often also plotted as an enrichment plot.

3. Ranking binding affinity: Most docking programs include a mechanisms for scoring how well a compound binds to an active site. This is often constructed from an empirical analysis of the binding and affinities of a set of known protein-ligand complexes. In general, it is found that the "fast" scoring functions implemented in most docking programs are unable to predict successfully the relative binding affinity of a set of compounds.

The specific algorithms used by rDock can be found here.

References

Publications describing rDock

Validation of an empirical RNA-ligand scoring function for fast flexible docking using RiboDock (R)

Author(s): Morley SD, Afshar M

Source: JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN 18 (3): 189-208 MAR 2004

Virtual screening in structure-based drug discovery

Author(s): Barril X, Hubbard RE, Morley SD

Source: MINI-REVIEWS IN MEDICINAL CHEMISTRY 4 (7): 779-791 SEP 2004

Publications using rDock for protein ligands

Identification of chemically diverse Chk1 inhibitors by receptor-based virtual screening

Author(s): Foloppe N, Fisher LM, Howes R, Potter A, Robertson AGS, Surgenor AE

Source: BIOORGANIC & MEDICINAL CHEMISTRY 14 (14): 4792-4802 JUL 15 2006

Structure-based discovery of a new class of Hsp90 inhibitors

Author(s): Barril X, Brough P, Drysdale M, Hubbard RE, Massey A, Surgenor A, Wright L

Source: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 15 (23): 5187-5191 DEC 1 2005

Structure-based design of novel Chk1 inhibitors: Insights into hydrogen bonding and protein-ligand affinity

Author(s): Foloppe N, Fisher LM, Howes R, Kierstan P, Potter A, Robertson AGS, Surgenor AE

Source: JOURNAL OF MEDICINAL CHEMISTRY 48 (13): 4332-4345 JUN 30 2005

Unveiling the full potential of flexible receptor docking using multiple crystallographic structures

Author(s): Barril X, Morley SD

Source: JOURNAL OF MEDICINAL CHEMISTRY 48 (13): 4432-4443 JUN 30 2005

Publications using rDock for RNA ligands

Towards the discovery of drug-like RNA ligands?

Author(s): Foloppe N, Matassova N, Aboul-Ela F

Source: DRUG DISCOVERY TODAY 11 (21-22): 1019-1027 NOV 2006

A structure-based strategy to identify new molecular scaffolds targeting the bacterial ribosomal A-site

Author(s): Foloppe N, Chen IJ, Davis B, Hold A, Morley D, Howes R

Source: BIOORGANIC & MEDICINAL CHEMISTRY 12 (5): 935-947 MAR 1 2004

The bacterial ribosome, a promising focus for structure-based drug design

Author(s): Knowles DJC, Foloppe N, Matassova NB, Murchie AIH

Source: CURRENT OPINION IN PHARMACOLOGY 2 (5): 501-506 OCT 2002