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DOCKTITE-A Highly Versatile Step-by-Step Workflow for Covalent Docking and Virtual Screening in the Molecular Operating Environment.

Scholz, Christoph and Knorr, Sabine and Hamacher, Kay and Schmidt, Boris (2015):
DOCKTITE-A Highly Versatile Step-by-Step Workflow for Covalent Docking and Virtual Screening in the Molecular Operating Environment.
In: Journal of chemical information and modeling, pp. 398-406, 55, (2), ISSN 1549-960X,
[Article]

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).

Item Type: Article
Erschienen: 2015
Creators: Scholz, Christoph and Knorr, Sabine and Hamacher, Kay and Schmidt, Boris
Title: DOCKTITE-A Highly Versatile Step-by-Step Workflow for Covalent Docking and Virtual Screening in the Molecular Operating Environment.
Language: English
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).

Journal or Publication Title: Journal of chemical information and modeling
Volume: 55
Number: 2
Divisions: 10 Department of Biology
10 Department of Biology > Computational Biology and Simulation
Date Deposited: 07 Apr 2015 06:48
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