Molecular modeling on solvent effect and interaction mechanism of fentanylanalogs to mu-opioid receptor

AIM: To do theoretical study about solvation effect and interaction mechani sm of f'entanyl analogs (FA) to mu opioid receptor (mu OR). METHODS: Flexib le docking (FlexiDock) was performed by using the possible active conformat ions of FA and optimized 3D structure of mu opioid receptor. Binding energi es were calculated. Comparative molecular force field analysis (CoMFA) and quantitative structure activity relationship (QSAR) studies were carried ou t based on results of flexible docking. Solvation effects were considered b y studying interaction of FA with water molecules. Partial least square (PL S) analysis was used to calculate regression equation for analgesic activit ies using binding energies as descriptive factor. RESULTS: 1) Binding confo rmations of these analogs derived by flexible docking were reasonable. 2) I t was most possible for the FA to exist in water solution in the form of bi nding conformations. 3) Energetic calculation and QSAR analysis showed a go od correlation between the calculated binding energies of FA and their anal gesic activities. 4) Based on the 3D-model, the possible interaction mechan ism of FA with mu opioid receptor can be illustrated reasonably. CONCLUSION : The nature of the correlation between the binding affinities and analgesi c activities of FA was explained by our modeling result.