Theoretical studies on opioid receptors and ligands. I. Molecular modeling and QSAR studies on the interaction mechanism of fentanyl analogs binding to ?-opioid receptor

Based on our previous result of the three-dimensional model of the μ-opioid receptor, binding conformations of 13 fentanyl analogs and three-dimensional structures for the complexs of these analogs with μ-opioid receptor were constructed employing the molecular modeling method and our binding conformation search program for ligands (BCSPL). Energetic calculation and quantitative structure–activity relationship (QSAR) analysis indicated a good correlation between the calculated binding energies of fentanyl analogs and their binding affinities, pKi's and pK's, and analgesic activities, − log ED50's. Based on the three-dimensional models, the possible interaction mechanism of fentanyl analogs with μ-opioid receptor can be illustrated and the available structure–activity relationship of these analgesic agents can be explained reasonably. © 2000 John Wiley & Sons, Inc. Int J Quant Chem 78: 285–293, 2000