DockBench: An Integrated Informatic Platform Bridging the Gap between the Robust Validation of Docking Protocols and Virtual Screening Simulations

Abstract

Virtual screening (VS) is a computational methodology that streamlines the drug discovery process by reducing costs and required resources through the in silico identification of potential drug candidates. Structure-based VS (SBVS) exploits knowledge about the three-dimensional (3D) structure of protein targets and uses the docking methodology as search engine for novel hits. The success of a SBVS campaign strongly depends upon the accuracy of the docking protocol used to select the candidates from large chemical libraries.The identification of suitable protocols is therefore a crucial step in the setup of SBVS experiments. Carrying out extensive benchmark studies, however, is usually a tangled task that requires users' proficiency in handling different file formats and philosophies at the basis of the plethora of existing software packages. We present here DockBench 1.0, a platform available free of charge that eases the pipeline by automating the entire procedure, from docking benchmark to VS setups. In its current implementation, DockBench 1.0 OPEN ACCESSMolecules 2015, 20 9978 handles seven docking software packages and offers the possibility to test up to seventeen different protocols. The main features of our platform are presented here and the results of the benchmark study of human Checkpoint kinase 1 (hChk1) are discussed as validation test.

Synthesis, structure-activity relationships and biological evaluation of 7-phenyl-pyrroloquinolinone 3-amide derivatives as potent antimitotic agents

“…Finally, Protonate 3D tool was used to assign the ionic state of each complex [28]. To identify the more appropriate docking protocol for the eleven complexes, we performed a self-docking benchmark using DockBench 1.01, a tool that compared the performance of 14 different posing/scoring protocols [29]. The active site was defined using a radius of 12 Å from the center of mass of the co-crystallized ligand.…”

The Influence of the 1-(3-Trifluoromethyl-Benzyl)-1H-Pyrazole-4-yl Moiety on the Adenosine Receptors Affinity Profile of Pyrazolo[4,3-e][1,2,4]Triazolo[1,5-c]Pyrimidine Derivatives

“…The workflow of the molecular docking approach used in the present work has been previously reported. [ 40 , 49 ] First of all, the role of the 1-(3-trifluoromethyl-benzyl)-1 H -pyrazole-4-yl moiety in receptor recognition has been investigated starting from the analysis of the hypothetical binding mode of CTV 6975 ( 1 ) and two other structurally similar analogues 36 and 33 [ 22 ] against all four AR subtypes ( Fig 5A ). In particular, compound 36 differs in the 1,3-disubstitution of the xanthine core, where the methyl groups of CVT 6975 ( 1 ) are replaced by two propyl groups.…”

Comparing Fragment Binding Poses Prediction Using HSP90 as a Key Study: When Bound Water Makes the Difference

“…A benchmark of 17 different docking protocols over 200 HSP90-ligand x-ray complexes was performed using DockBench [ 36 ] to select the most suitable protocol (details are provided in the Suplementary Material). The results were in agreement with previously reported docking studies on HSP90 [ 37 ].…”