Improving VEGFR-2 Docking-Based Screening by Pharmacophore Postfiltering and Similarity Search Postprocessing

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• 作者：Jesu虂s M. Planesas ; Rosa M. Claramunt ; Jordi Teixido虂 ; Jose虂 I. Borrell ; Violeta I. Pe虂rez-Nueno
• 刊名：Journal of Chemical Information and Modeling
• 出版年：2011
• 出版时间：April 25, 2011
• 年：2011
• 卷：51
• 期：4
• 页码：777-787
• 全文大小：1051K
• 年卷期：v.51,no.4(April 25, 2011)
• ISSN：1549-960X

文摘

Conventional docking-based virtual screening (VS) of chemical databases is based on the ranking of compounds according to the values retrieved by a scoring function (typically, the binding affinity estimation). However, using the most suitable scoring function for each kind of receptor pocket is not always an effective process to rank compounds, and sometimes neither to distinguish between correct binding modes from incorrect ones. To improve actives from decoys selection, here we propose a three-step VS protocol, which includes the conventional docking step, a pharmacophore postfilter step, and a similarity search postprocess. This VS protocol is retrospectively applied to VEGFR-2 (Kdr-kinase) inhibitors. The resulting docking poses calculated using the Alpha HB scoring function implemented in MOE are postfiltered according to defined pharmacophore interactions (structure based). The selected poses are again ranked according to their molecular similarity (MACCS fingerprint) to the cognate ligand. Results show that both the overall and early VS performance improve the application of this protocol.