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

研究成果: 雜誌貢獻文章

3 引文 斯高帕斯(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.

頁(從 - 到)272-281
期刊Chemical Biology and Drug Design
出版狀態已發佈 - 2017 八月 1


ASJC Scopus subject areas

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