Structure-based pharmacophore modeling and virtual screening to identify novel inhibitors for anthrax lethal factor

Huang Sheng Liao, Hsuan Liang Liu, Wei Hsi Chen, Yih Ho

研究成果: 雜誌貢獻文章同行評審

6 引文 斯高帕斯(Scopus)

摘要

Inhibition of anthrax lethal factor (LF) has been reported to be a potent strategy for the treatment of anthrax; however, no effective LF inhibitors are currently available. In this study, a structure-based pharmacophore model was developed based on the co-crystallized structure of anthrax LF with the active inhibitor GM6001. The best pharmacophore model (denoted as SB-Hypo1), consisting of two hydrogen bond acceptors, one hydrogen bond donor and one hydrophobic, was further validated using Gunner-Henry score method. The well-validated SB-Hypo1 was then used as a 3D-query in virtual screening to identify potential hits from NCI database. These hits were subsequently filtered by ADMET and validated by molecular docking experiments, and their binding stabilities were validated by 10-ns MD simulations. Finally, three hits were identified as potential leads based on their favorable binding interactions.

原文英語
頁(從 - 到)3725-3732
頁數8
期刊Medicinal Chemistry Research
23
發行號8
DOIs
出版狀態已發佈 - 八月 2014

ASJC Scopus subject areas

  • 藥理學、毒理學和藥劑學 (全部)
  • 有機化學

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