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

• Published in: Molecules (Basel, Switzerland) Vol. 20; no. 6; pp. 9977 - 9993
• Main Authors: Cuzzolin, Alberto, Sturlese, Mattia, Malvacio, Ivana, Ciancetta, Antonella, Moro, Stefano
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29-05-2015; MDPI
• Subjects: Accuracy; Algorithms; Automation; Benchmarking; Binding sites; Cell cycle; Checkpoint Kinase 1; Docking; docking benchmark; Drug Design; Drug Discovery; Drugs; High-Throughput Screening Assays; Humans; Kinases; Ligands; Methodology; molecular docking; Molecular Docking Simulation; Platforms; Protein Binding; Protein Conformation; Protein Kinase Inhibitors - chemistry; Protein Kinases - chemistry; Small Molecule Libraries - chemistry; Software; Software packages; Structure-Activity Relationship; structure-based drug design; Three dimensional; User interface; User-Computer Interface; virtual screening; Visualization; structure-based drug design; docking benchmark; molecular docking; virtual screening
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules20069977

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 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.