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

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3725-3732
Number of pages8
JournalMedicinal Chemistry Research
Volume23
Issue number8
DOIs
Publication statusPublished - 2014

Fingerprint

Hydrogen
Hydrogen bonds
Screening
Anthrax
Databases
Experiments
anthrax toxin
N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide

Keywords

  • Anthrax lethal factor
  • Gunner-Henry score
  • MD simulations
  • Pharmacophore model
  • Virtual screening

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

Cite this

Structure-based pharmacophore modeling and virtual screening to identify novel inhibitors for anthrax lethal factor. / Liao, Huang Sheng; Liu, Hsuan Liang; Chen, Wei Hsi; Ho, Yih.

In: Medicinal Chemistry Research, Vol. 23, No. 8, 2014, p. 3725-3732.

Research output: Contribution to journalArticle

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