在前期研究基础上，结合最新报道的GPCR受体晶体结构及荧光标记方法，本项目将深入开展基于小分子高活性化合物结构和AST受体结构的多肽类农药创新研究。主要包括三个方面：1）高活性化合物的结构优化研究：针对高活性模拟肽H17及非肽化合物B1，利用模拟肽学及农药分子设计方法，通过结构优化及构效关系研究，以期发现结构更简单、有前景的候选IGRs；2）模拟肽的活性构象研究：采用2D-NMR和分子动力学（MD）方法开展化合物的构象研究，验证前期关于"linear"可能是活性构象的假设，以明确模拟肽的活性构象；3）模拟肽与不同受体之间作用模式研究：以最新报道的鼠μ-肽受体和人肽受体GPCR晶体结构为新模板蛋白，构建Dippu-AstR、DAR-1和DAR-2三种AST的三维结构。采用分子对接及MD方法分析活性模拟肽与受体结合的活性构象，探索它们与不同受体之间的作用模式，以发现更高活性的模拟肽IGRs.

Based on our preliminary results, the latest crystal structure of GPCR and the quantitative assay using fluorescent tags, this project will continue to discover new peptide mimetic IGRs considering both structures of active AST mimics and AST receptor. The story includes three parts as follows: 1）The optimization of high active compounds: Compound H17 and B1, discovered in our former work, will be structurally optimized with the method of peptidomimatics and pesticide molecular design to find new perspective IGRs candidates with simpler structure and higher activity; 2）The study on active conformation of peptide mimics：the conformation of various peptide analogs will be analysized by 2D-NMR and molecular dynamics with the purpose of testing and verifying the preliminary hypothesis as that "linear" may be the active conformation；3）The study on the interaction between peptide analogs and AST receptors：Choosing the Crystal structure of the μ-opioid receptor and the nociceptin/orphanin FQ receptor as new model protein, the 3D- structures of three AST receptors, Dippu-AstR、DAR-1 and DAR-2, will be built with homology modeling method. The active conformation of analogs and their interaction with receptors will be studied by molecular docking and molecular dynamics. The results will be useful for further discovery of new higher IGRs.