Homology Modeling of the Mysid Ecdysone Receptor and Docking Simulation with Ecdysteroids

The ecdysone receptor (EcR) belongs to the nuclear-hormone receptor superfamily that functions as a ligand-activated transcription factor. The EcR plays an essential role in arthropod development and reproduction. While the molecular basis for the interaction between the EcR and its ligand has been well investigated in insects, information on the EcR function in crustaceans is limited. In the present study, a three-dimensional model of the ligand-binding domain (LBD) of the mysid EcR was built based on the X-ray crystal structure of the insect EcR LBD bound to ponasterone A and docking simulations of endoand exogenous ecdysteroids including ecdysone, 20-hydroxyecdysone, ponasterone A, muristerone A and tebufenozide were performed. In silico simulations demonstrated that these ecdysteroids efficiently docked with the active site of mysid EcR LBD. The relative potencies based on the interaction energy were in the order of ponasterone A > muristerone A > 20hydroxyecdysone > tebufenozide > ecdysone. These results suggest that this in silico assay may be a useful initial screening tool for potential EcR ligands.