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| About Johannes H. Voigt (Schering Plough) |
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Johannes Voigt was born in Oldenburg, Germany. He received his Diploma in Organic Chemistry in 1993 and a PhD in Chemistry in 1997 from the University of Göttingen, Germany. In 1997 he moved to Bethesda, MD where he joined the Computer Aided Drug Design group of the Laboratory of Medicinal Chemistry at the National Cancer Institute (NCI). Johannes stayed for three years at NCI, where he worked with Drs. Bill Milne and Marc Nicklaus. He joined the Schering-Plough Research Institute in 2001, where he currently is a Principal Scientist in the Drug Design group of the Department of Medicinal Chemistry. His scientific fields of expertise within computational chemistry include – but are not limited to – molecular modeling, ab initio calculations, chemoinformatics, and structure-based drug design.
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Cross-docking to CDK2: a Virtual Screening Study
Johannes H. Voigt, Vincent S. Madison, Jose S. Duca ; Department of Drug Design, Schering-Plough Research Institute, 2015 Galloping Hill Road, K15-1-1800, Kenilworth, New Jersey 07033, USA
We recently published a comprehensive cross docking study on CDK2 covering the analysis of docking accuracy and score/affinity correlations for a uniform set of 150 CDK2 crystal structures (Duca, Voigt, J. Chem. Inf. Model. 2008, 48, 659-668 and 669-678). In agreement with previous docking/scoring evaluations, the docking accuracy of Gold and Glide was good, while the score/affinity correlations were not satisfactory.
In this study virtual screening for this unique data set was investigated. The following questions were addressed: A) Does virtual screening for this data set work? B) If yes, does it work for the correct reasons? Here it is valuable to have the experimentally determined binding modes of the active ligands. C) What is the best choice of the decoy set, what really is a decoy, and is a decoy set only valid in the context of the active molecules? In comparison to our in-house ligands, the DUD CDK2 data set was used (“Benchmarking Sets for Molecular Docking” Huang, N., Shoichet, B.K., Irwin, J.J., J. Med. Chem. 2006, 49, 23, 6789 - 6801.) D) Does combing of docking results from multiple protein structures enhance the performance? E) How do Gold and Glide compare?
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