title: DOCKTITE-a highly versatile step-by-step workflow for covalent docking and virtual screening in the molecular operating environment.
abstract: The formation of a covalent bond with the target is essential for a number of successful drugs, yet tools for covalent docking without significant restrictions regarding warhead or receptor classes are rare and limited in use. In this work we present DOCKTITE, a highly versatile workflow for covalent docking in the Molecular Operating Environment (MOE) combining automated warhead screening, nucleophilic side chain attachment, pharmacophore-based docking, and a novel consensus scoring approach. The comprehensive validation study includes pose predictions of 35 protein/ligand complexes which resulted in a mean RMSD of 1.74 Å and a prediction rate of 71.4% with an RMSD below 2 Å, a virtual screening with an area under the curve (AUC) for the receiver operating characteristics (ROC) of 0.81, and a significant correlation between predicted and experimental binding affinities (ρ = 0.806, R(2) = 0.649, p < 0.005).
authors.affiliation: Clemens Schöpf-Institute of Organic Chemistry and Biochemistry, Technische Universität Darmstadt , Alarich-Weiss-Strasse 4, 64287 Darmstadt, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Scholz
authors.forename: Sabine
authors.initials: S
authors.lastname: Knorr
authors.forename: Kay
authors.initials: K
authors.lastname: Hamacher
authors.forename: Boris
authors.initials: B
authors.lastname: Schmidt
mesh_terms: D000465:Algorithms; D019540:Area Under Curve; D001895:Boron / Q000737:chemistry; D005857:Germanium / Q000737:chemistry; D057166:High-Throughput Screening Assays / Q000379:methods*; D008024:Ligands; D008958:Models, Molecular; D062105:Molecular Docking Simulation / Q000379:methods*; D011237:Predictive Value of Tests; D011485:Protein Binding; D012372:ROC Curve; D015203:Reproducibility of Results; D013635:Tantalum / Q000737:chemistry; D057188:Workflow; D014961:X-Ray Diffraction
chemical_list: D008024:Ligands; D005857:Germanium; D013635:Tantalum; D001895:Boron