基于抗体的免疫分析技术是快速检测农兽药、保障食品安全的重要手段，但农兽药免疫原性弱、单抗制备周期长，要求抗体对有机溶剂具有一定耐受性；因此，本项目拟以稳定性好（耐受116℃和6mol/L盐酸胍）的嗜热菌精氨酸结合蛋白（TmArgBP）为骨架，利用核糖体展示技术实现大容量快速筛选，结合计算生物学技术设计多位点组合随机突变，构建核糖体展示TmArgBP突变模拟抗体库，以典型农兽药己烯雌酚、对硫磷、百草枯等不同小分子为靶标，建立虚拟筛选为辅、生物淘筛为主高稳定性抗体快速筛选技术，阐释TmArgBP高稳定识别靶标机制，进行多轮快速淘筛并高效功能表达，获得农兽药高稳定性模拟抗体，系统评价快速筛选制备TmArgBP模拟抗体的可行性，为高稳定性抗体制备奠定技术基础并提供方法学支撑。本项目是食品安全、计算生物学、生物技术多学科交叉研究，在进出口检验检疫、食品安全、质量监督、临床检测等领域具有广阔应用前景。

Antibody-based immunoassay is a significant measure for the rapid detection of pesticide and veterinary drug residues and ensuring safety of food. However, on one hand, It proved to be difficult and costly for preparing the monoclonal antibody of pesticide and veterinary drug residues because of its weak immunogenicity. On the other hand, the important demand for antibody is highly stable in low concentration organic solvents when in the detection of pesticide and veterinary drug residues. Aims to achieve rapid screening and to acquire highly stable antibody, arginine-binding protein from Thermotoga maritima(TmArgBP) with a good thermal stability (resistance to 116 ℃) and chemical stability ( resistance to 6M guanidine hydrochloride ) was select as protein skeleton materials and multi-site random mutations were carried out by computational biology technology in its ligand binding region for the construction of ribosome display library. Targeted typical pesticide and veterinary drug residues such as diethylstilbestrol, parathion and paraquat, the mimic antibodies will be acquired based on the biopanning technology and virtual screening and are functionally expressed. The properties of mimic antibodies are overall evaluated and identified. Then the mechanism for the high stability of TmArgBP and for the function of amino acid sites in ligand binding region is elucidated. The rapid screening methods could be established for the preparation of highly stable antibody of pesticide and veterinary drug residues. This project is multidisciplinary research of food safety, computational biology and biology technology. And it has broad future application in the field of inspection and quarantine of the imports and exports, food safe and quality supervision and clinical examination.