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

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/

Reliability analysis and optimization of the consensus docking approach for the development of virtual screening studies

“…Three different docking software were selected for this analysis: GLAMDOCK 47 , PLANTS (Protein-Ligand ANT System) 48 and rDOCK 49 . Three different EF evaluations were thus carried out, each employing 9 docking methods for pose clustering and consensus level calculations, i.e.…”

“…This docking software uses a combination of stochastic and deterministic search techniques to generate low energy ligand poses 49 . The docking protocol generates a single ligand pose using 3 stages of Genetic Algorithm search (GA1, GA2, GA3), followed by low temperature Monte Carlo (MC) and Simplex minimization (MIN) stages.…”

Structure-Based Discovery of Small Molecules Binding to RNA

“…Li et al obtained similar results for Glide and GOLD using a test set of 60 RNA-ligand complexes (60 and 62%, respectively) [70]. On a test set composed of 56 RNA-ligand complexes, in 54% of the cases rDOCK was able to predict the correct binding mode while AutoDock Vina and Glide obtained success rates of 29 and 18%, respectively [64]. For MODOR, a success rate of 74% (based on a data set of 57 complexes), for RiboDock 50% (out of 10 complexes), and for ICM 53% was found (test set containing 96 complexes) [72,73,75].…”

“…It contains an empirical scoring function which includes terms for typical RNA-ligand interactions such as guanidinium-RNA interactions and π-π stacking of aromatic rings in addition to terms found in conventional functions such as hydrogen-bond and lipophilic interactions. The program rDock has evolved from RiboDock and is applicable for protein and RNA targets [64]. A GA is used to generate an initial docking pose which is refined using MC simulations.…”

Shogaol–huprine hybrids: Dual antioxidant and anticholinesterase agents with β-amyloid and tau anti-aggregating properties

“…51 Docking of AChE inhibitors was performed using the rDock program. 52 A cavity of radius 17 Å, centered on the structure of a superligand containing huprine X, donepezil and propidium (as found in the X-ray structures 1E66, 1EVE and 1N5R) was used to define the docking volume. Since huprine X and propidium are bound to the catalytic and the peripheral binding sites, and donepezil is aligned along the gorge, this definition guarantees the exploration of the binding mode along the whole volume accessible for binding.…”