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

被引：160

作者：

Scholz, Christoph ^{[1
]}

Knorr, Sabine ^{[2
]}

Hamacher, Kay ^{[2
]}

Schmidt, Boris ^{[1
]}

机构：

[1] Tech Univ Darmstadt, Clemens Schopf Inst Organ Chem & Biochem, D-64287 Darmstadt, Germany

[2] Tech Univ Darmstadt, D-64287 Darmstadt, Germany

来源：

JOURNAL OF CHEMICAL INFORMATION AND MODELING | 2015年 / 55卷 / 02期

关键词：

FORCE FIELD; INHIBITORS; DISCOVERY; BINDING; POTENT; ENERGY;

D O I：

10.1021/ci500681r

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 angstrom and a prediction rate of 71.4% with an RMSD below 2 angstrom, 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 (rho = 0.806, R-2 = 0.649, p < 0.005).

引用

收藏

页码：398 / 406

页数：9

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