A molecular dynamics approach to identify an oxysterol-based hedgehog pathway inhibitor

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• 作者：Radha Charan Dash ; Chad R. Maschinot ; M. Kyle Hadden ; ^{kyle.hadden@uconn.edu}
• 关键词：Hedgehog signaling ; Smoothened ; Cysteine-rich domain ; Oxysterols ; Molecular dynamics
• 刊名：Biochimica et Biophysica Acta (BBA) - General Subjects
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：1861
• 期：2
• 页码：168-177
• 全文大小：1720 K
• 卷排序：1861

文摘

A homology model of the N-terminal cysteine rich domain of the Smoothened receptor was generated. Molecular dynamics and binding energy calculations of the model in complex with a series of oxysterols were performed. Hh modulatory activity correlated well with predicted binding energy: Hh antagonists were predicted to bind with high energy and Hh agonists were predicted to bind with low energy. These computational studies led to the identification of a new Hh inhibitor with the oxysterol scaffold.