Acta Phys. -Chim. Sin. ›› 2010, Vol. 26 ›› Issue (01): 206-214.doi: 10.3866/PKU.WHXB20100117

• BIOPHYSICAL CHEMISTRY • Previous Articles     Next Articles

Molecular Docking and Molecular Dynamics Simulations of Fentanyl Analogs Binding to μ-Opioid Receptors

LI Bo, LIU Ming, HU Wen-Xiang   

  1. Institute of Physical Organic and Medicinal Chemistry, Capital Normal University, Beijing 100048, P. R. China; College of Life Science, Capital Normal University, Beijing 100048, P. R. China
  • Received:2009-05-08 Revised:2009-09-08 Published:2009-12-29
  • Contact: HU Wen-Xiang


We performed molecular docking andmolecular dynamics (MD) simulations to investigate the interactions between fentanyl analogs and μ-opioid receptors. The AutoDock 4.0 program was used to perform the docking and homology modeling of the μ-opioid receptor structure. MD method as implemented in the GROMACS program was used to model the twelve fentanyl receptor agonists and the μ-opioid receptor protein compounds in water and to optimize the docking complex structure. Based on MM-PBSA methods, the APBS program was used to calculate the binding affinity of the complexes and the binding contant of receptor and liqand (Ki) values determined using MM-PBSA were consistent with the experimental values. Our predictions of compound activity sequences were, therefore, correct. The MD simulations of these complexes revealed that the protein structures in the complexes differed substantially from the structures of the ligand-free receptors. The backbone of the intracellular region segments IL2, IL3 and TM4 showed that the skeleton conformations had changed significantly. Different compounds may influence the receptor structure differently. Compounds with high activities may enhance binding flexibility in certain protein structural regions. These facts imply that fentanyl analogs may result in μ-opioid receptors changing to an active conformation after receptor binding. Physiologic effects may thus be triggered by a mediating signal transduction and by the activation of the G-protein.

Key words: Molecular dynamics, Fentanyl, μ-opioid receptor, Molecular docking


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