Molecular modeling of interaction between delta opioid receptor and 3-methylfentanylisothiocyanate

Abstract

Aim: To construct a 3D structural model of delta opioid receptor (delta OR) and study its interaction with 3-methylfentanylisothiocyanate (SuperFIT).

Methods: Using the bacteriohodopsin as a template, the 3D structure of delta OR was modeled; SuperFIT was docked into its inside.

Results: The interaction model between delta OR and (3R, 4S)-SuperFIT was achieved, in which the important binding sites possibly were Asp128, Ser106, Phe104, Tyr308, and Pro315. Asp128 formed the electrostatic and hydrogen-binding interactions with the protonated nitrogen on piperidine of the ligand. Ser106 formed the electrostatic interaction with the N atom of isothiocyano group of the ligand; whereas Phe104, Tyr308, and Pro315 formed the hydrophobic interactions with the S atom of isothiocyano group. In addition, there were some other interactions between delta OR and the ligand.

Conclusion: The residues Phe104, Tyr308, Pro315, and Ser106 of delta OR are crucial to the delta selectivity of the ligand, which is beneficial for designing novel delta-selective ligand.