Insight into the binding model of new antagonists of kappa receptor using docking and molecular dynamics simulation

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• 作者：Shiyuan Hu (1)
  Haijing Yu (1)
  Yongjuan Liu (1)
  Tian Xue (1)
  Huabei Zhang (1)
  
• 关键词：Kappa receptor ; Docking ; Molecular dynamics simulation ; MM ; GB/SA
• 刊名：Journal of Molecular Modeling
• 出版年：2013
• 出版时间：August 2013
• 年：2013
• 卷：19
• 期：8
• 页码：3087-3094
• 全文大小：688KB
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• 作者单位：Shiyuan Hu (1)
  Haijing Yu (1)
  Yongjuan Liu (1)
  Tian Xue (1)
  Huabei Zhang (1)
  
  1. Key Laboratory of Radiopharmaceuticals of Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, 100875, China
  

文摘

PF-4455242 and its analogues represent a new series of kappa opioid selective antagonists that demonstrate high selectivity and potency. We investigated their binding mode to the κ-receptor via docking and molecular dynamics simulations. The ranking of the predicted binding free energies is consistent with experimental results. Detailed binding free energies between antagonists and individual protein residues were calculated, and key residues involved in binding were identified. Deviation of the active site residues was investigated, and the results show that Gln115, Leu135, Tyr139, Trp287 and Tyr313 deviate greatly from the reference structure. Information obtained from molecular modeling studies will aid in the design of potent kappa receptor antagonists.