An ecdysone receptor (EcR) is a nuclear receptor protein, a prime target for pesticide development processes due to its involvement in the growth and development of insects. The activation of EcRs leads to hasty and premature development of insects, thereby preventing them from destroying the crops. The high cost, environmental toxicity, and resistance towards the currently available insecticides have resulted in a growing demand for the development of economical and environment-friendly pesticides with unique insecticidal activity. Several reports on resistance towards conventional pesticides like ponasterone A and RH-5849 were reported in recent years. In this study, the plant derived (C. deodara), in-house synthesized molecules with benzosuberene scaffolds were screened for their ability to interact with the EcRs of both Hemiptera and Coleoptera. The preliminary analysis by molecular docking showed that some of our molecules exhibited excellent binding with the target protein. Moreover, molecular dynamics simulations, binding free energy estimations, and umbrella sampling simulations were conducted to validate the docking results. Our analysis revealed Com-7 and Com-3 as potential EcR agonists to target Hemiptera and Coleoptera, respectively. Also, Com-8 and Com-12 could be used as lead compounds against the EcR of Coleoptera.

中文翻译：

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新的蜕皮激素受体激动剂：一种合理发现作物保护杀虫剂的计算方法

蜕皮激素受体 (EcR) 是一种核受体蛋白，由于其参与昆虫的生长和发育，因此是农药开发过程的主要目标。EcR 的激活导致昆虫过早发育，从而防止它们破坏作物。成本高、环境毒性和对现有杀虫剂的耐药性导致对开发具有独特杀虫活性的经济、环保的农药的需求不断增长。近年来报道了一些关于对传统农药如松甾酮 A 和 RH-5849 的抗性的报道。在这项研究中，植物衍生的（C. deodara)，筛选了具有苯并丁二烯支架的内部合成分子与半翅目和鞘翅目的 EcR 相互作用的能力。分子对接的初步分析表明，我们的一些分子与目标蛋白表现出极好的结合。此外，还进行了分子动力学模拟、结合自由能估计和伞状采样模拟以验证对接结果。我们的分析显示 Com-7 和 Com-3 分别是针对半翅目和鞘翅目潜在的 EcR 激动剂。此外，Com-8 和 Com-12 可用作对抗鞘翅目 EcR 的先导化合物。