rDock: A Fast, Versatile and Open Source Program for Docking Ligands to Proteins and Nucleic Acids

TLDR

Identification of chemical compounds with specific biological activities is a key step in chemical biology and drug discovery, and when target structures are available, molecular docking programs assess chemical complementarity to rank compounds in virtual screening; rDock, developed at Vernalis for high‑throughput virtual screening, exemplifies this approach. This article provides an overview of rDock’s structure and features and compares it to the open‑source AutoDock Vina and the commercial Schrödinger Glide. rDock, evolved from RiboDock, is a computationally efficient docking program for proteins and nucleic acids that uses target structures to assess chemical complementarity, allows biasing with additional constraints, and is freely available under the LGPL with manuals, examples, and test sets at rdock.sourceforge.net. rDock is faster than Vina and comparable to Glide in virtual‑screening speed, outperforms Glide in binding‑mode prediction, and achieves better VS performance than Vina but is generally inferior to Glide unless pharmacophore constraints are applied, at which point rDock and Glide perform equally.

Abstract

Identification of chemical compounds with specific biological activities is an important step in both chemical biology and drug discovery. When the structure of the intended target is available, one approach is to use molecular docking programs to assess the chemical complementarity of small molecules with the target; such calculations provide a qualitative measure of affinity that can be used in virtual screening (VS) to rank order a list of compounds according to their potential to be active. rDock is a molecular docking program developed at Vernalis for high-throughput VS (HTVS) applications. Evolved from RiboDock, the program can be used against proteins and nucleic acids, is designed to be computationally very efficient and allows the user to incorporate additional constraints and information as a bias to guide docking. This article provides an overview of the program structure and features and compares rDock to two reference programs, AutoDock Vina (open source) and Schrödinger's Glide (commercial). In terms of computational speed for VS, rDock is faster than Vina and comparable to Glide. For binding mode prediction, rDock and Vina are superior to Glide. The VS performance of rDock is significantly better than Vina, but inferior to Glide for most systems unless pharmacophore constraints are used; in that case rDock and Glide are of equal performance. The program is released under the Lesser General Public License and is freely available for download, together with the manuals, example files and the complete test sets, at http://rdock.sourceforge.net/