Adipokinetic hormone (AKH) is an insect neuropeptide that plays crucial roles in a variety of physiological functions such as regulation of heartbeat frequency, blood hemolymph trehalose levels, and protein synthesis. It exerts its functions through binding to its cognate G protein-coupled receptor (GPCR), named adipokinetic hormone receptor (AKHR). The aim of this study is to characterize AKHR of stick insect, Carausius morosus, which becomes an agricultural and forest pest during its outbreaks, and to screen pesticide candidates that would act through inhibition of AKHR. To this aim, the sequence of the receptor and its ligand were obtained from previously published transcriptome data and homology modeling, molecular docking, and molecular dynamics (MD) simulations were combined to find the ligand-binding pocket of AKHR. As a result, crucial residues in ligand binding were identified. These residues were located at the 6th and 7th transmembrane (TM) domains and the 2nd extracellular loop (ECL) of AKHR model. In order to propose pesticide candidates, virtual screening was performed, and candidate ligands were obtained. Considering the binding energies and the stability of the interaction between the ligand and the receptor, four hit compounds were selected. In conclusion, this study revealed a possible ligand-binding pocket of AKHR and proposed some high-affinity small-molecules to block its function, which would further facilitate pesticide design studies against the same receptor of various pests.

脂肪代谢激素（AKH）是一种昆虫神经肽，在多种生理功能（例如心跳频率，血液血淋巴海藻糖水平和蛋白质合成）的调节中起着至关重要的作用。它通过与同种的G蛋白偶联受体（GPCR）称为脂肪代谢激素受体（AKHR）结合而发挥功能。这项研究的目的是表征粘虫Carausius morosus的AKHR，在疫情暴发期间成为农业和森林害虫，并筛选可通过抑制AKHR发挥作用的农药候选物。为此，从先前公开的转录组数据中获得了受体及其配体的序列，并进行了同源建模，分子对接和分子动力学（MD）模拟，以找到AKHR的配体结合口袋。结果，鉴定了配体结合中的关键残基。这些残基位于AKHR模型的第六和第七跨膜（TM）域和第二细胞外环（ECL）。为了提出农药候选物，进行了虚拟筛选，并获得了候选配体。考虑到结合能和配体与受体之间相互作用的稳定性，选择了四种命中化合物。结论，