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| About Natasja Brooijmans (Wyeth) |
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Natasja Brooijmans obtained a Master's in Pharmacy from Utrecht University in The Netherlands. Thesis research for the M.Pharm. degree was done at Columbia University in Barry Honig's lab. In 1999, she joined the Chemical and Chemical Biology graduate program at the University of California San Francisco to pursue a Ph.D. After her graduation she joined Wyeth in Pearl River, where she has been since 2004. Research interests, beyond supporting drug discovery projects and applying structure-based drug design tools, include virtual screening, scoring, and ADME predictions.
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Realistic Virtual Screening Assessment in Kinases
Natasja Brooijmans, Wyeth
Most retrospective receptor-based virtual screening studies in the literature enrich libraries with highly-active compounds against the studied targets. While these studies show that docking can be used successfully to distinguish active ligands among decoys, these are not very realistic. In industrial settings, corporate and commercial collections are screened that contain very few optimized compounds that inhibit the target of interest in the nanomolar range. Leads identified by high-throughput screening and virtual screening are generally in the low-to-medium micromolar range. Using Glide SP docking, we have performed studies on a set of kinase targets that show that identifying these weak leads is significantly more difficult than identifying highly-optimized ligands. Enrichment Factors obtained with Glide4.0 and 4.5 will be compared. Finally, the use of pre- and post-docking filters to enhance Enrichment Factors was investigated.
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