Investigation of the bindings of a class of inhibitors with GSK3β kinase using thermodynamic integration MD simulation and kinase assay

Chia Jen Hsu, Wen Chi Hsu, Der Jay Lee, An Lun Liu, Chia Ming Chang, Huei Jhen Shih, Wun Han Huang, Guey Jen Lee-Chen, Hsiu Mei Hsieh-Li, Guan Chiun Lee, Ying Chieh Sun

Research output: Contribution to journalArticle

2 Citations (Scopus)


GSK3β kinase is a noteworthy target for discovery of the drugs that will be used to treat several diseases. In the effort to identify a new inhibitor lead compound, we utilized thermodynamic integration (TI)-molecular dynamics (MD) simulation and kinase assay to investigate the bindings between GSK3β kinase and five compounds that were analogous to a known inhibitor with an available crystal structure. TI-MD simulations of the first two compounds (analogs 1 and 2) were used for calibration. The computed binding affinities of analogs 1 and 2 agreed well with the experimental results. The rest three compounds (analogs 3–5) were newly obtained from a database search, and their affinity data were newly measured in our labs. TI-MD simulations predicted the binding modes and the computed ΔΔG values have a reasonably good correlation with the experimental affinity data. These newly identified inhibitors appear to be new leads according to our survey of GSK3β inhibitors listed in recent review articles. The predicted binding modes of these compounds should aid in designing new derivatives of these compounds in the future.

Original languageEnglish
Pages (from-to)272-281
Number of pages10
JournalChemical Biology and Drug Design
Issue number2
Publication statusPublished - 2017 Aug 1



  • GSK3β kinase
  • MD simulation
  • enzyme assay
  • inhibitor
  • thermodynamic integration

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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