title: DockBench as docking selector tool: the lesson learned from D3R Grand Challenge 2015.
abstract: Structure-based drug design (SBDD) has matured within the last two decades as a valuable tool for the optimization of low molecular weight lead compounds to highly potent drugs. The key step in SBDD requires knowledge of the three-dimensional structure of the target-ligand complex, which is usually determined by X-ray crystallography. In the absence of structural information for the complex, SBDD relies on the generation of plausible molecular docking models. However, molecular docking protocols suffer from inaccuracies in the description of the interaction energies between the ligand and the target molecule, and often fail in the prediction of the correct binding mode. In this context, the appropriate selection of the most accurate docking protocol is absolutely relevant for the final molecular docking result, even if addressing this point is absolutely not a trivial task. D3R Grand Challenge 2015 has represented a precious opportunity to test the performance of DockBench, an integrate informatics platform to automatically compare RMDS-based molecular docking performances of different docking/scoring methods. The overall performance resulted in the blind prediction are encouraging in particular for the pose prediction task, in which several complex were predicted with a sufficient accuracy for medicinal chemistry purposes.
authors.affiliation: Molecular Modeling Section (MMS), Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, Padua, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Salmaso
authors.affiliation: Molecular Modeling Section (MMS), Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, Padua, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Sturlese
authors.affiliation: Molecular Modeling Section (MMS), Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, Padua, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Cuzzolin
authors.affiliation: Molecular Modeling Section (MMS), Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, Padua, Italy. stefano.moro@unipd.it.
authors.forename: Stefano
authors.identifier: 0000-0002-7514-3802
authors.initials: S
authors.lastname: Moro
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D015195:Drug Design; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry; D006801:Humans; D008024:Ligands; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D018841:HSP90 Heat-Shock Proteins; D008024:Ligands; D011506:Proteins
keywords: Blind prediction; D3R Grand Challenge 2015; DockBench; Docking benchmark; Molecular docking