Ariadne merione ecdysone receptor (AmEcR) protein: An in silico approach for comparison of agonist and antagonist compounds

Abstract

Ecdysteroid signal transduction plays a major role in insect metamorphosis, 20-hydroxyecdysone (20E) binds to the nuclear receptor composed of the ecdysone receptor ligand binding domine (EcR-LBD) and triggers the developmental transitions. Ariadne merione ecdysone receptor (AmEcR) cDNA was amplified and partially sequenced of about 553 bp, which encodes a polypeptide of 184 amino acids (aa). The theoretical molecular weight (MW), isoelectric point (pI) and aliphatic index of the deduced AmEcR protein were predicted using BIOEDIT (v7.2.5) to be 21.192 kDa, 9.31 and 101.739 respectively. Identified ecdysone receptor gene of A. merione showed maximum similarity with Precis coenia gene. In this research, we have employed ligand-receptor engineering technique to screen a specific compound which plays antagonist role and assist to formulate an insect specific pesticide. The EcR protein 3D structure of AmEcR modeled using Schrödinger maestro and virtual screening was performed using 5554 molecules from Zinc database, where ZINC20031812 showed highest glide score of −6.257 and Etoxazole chosen on literature basis and showed best glide score −6.671. We have compared the antagonist with agonist (20E) by molecular dynamics (MD) simulation. Root Mean Square Deviation (RMSD) value of agonist and antagonist indicates the binding were stable in water with a range of distance from 2.3 to 2.6 Å, 1.8 to 2.3 Å and 1.9 to 2.3 Å with a variation over the time scale of 1 ps. Since Etoxazole and ZINC20031812 are antagonists, computationally they were more stable than 20E.