干旱胁迫已成为制约全球作物产量的重要因素之一，脱落酸（ABA）可调节气孔开度，是植物应对干旱胁迫的一种重要激素分子。ABA通过促进其受体蛋白与蛋白磷酸酶2C（PP2C）的相互作用来调控去磷酸化，然而该受体蛋白家族成员众多，ABA可调控多组受体与PP2C的相互作用，开启了多条信号通路，是造成影响其它生理表型的一个重要原因。特异性地调控ABA受体蛋白和PP2C的相互作用可有效解决该问题。因此，如何设计特异性调控PP2C蛋白去磷酸化的探针并揭示其分子机制是一个关键科学问题。本项目将综合运用计算化学、合成化学、化学生物学和结构生物学等方法，以前期发现的2种可特异性调控ABA受体蛋白与PP2C相互作用的分子探针为基础，通过“计算模拟－探针设计－作用机制”的研究循环，力争发现特异性调控ABA受体影响PP2C蛋白去磷酸化的化学探针并揭示其分子机制，为进一步开发可施用于农业的植物抗旱调节剂奠定基础。

Drought stress has grown to be one of the important factors to restrict global crop production. Abscisic acid (ABA), an important regulating factor for plant to antagonize drought stress, can reduce stomatal conductance to inhibit transpiration. ABA can regulate the dephosphorylation of protein phosphatase 2C (PP2C) by inducing the interaction between pyrabactin resistance (PYR)/PYR-like (PYL)/regulatory component of ABA receptor (RCAR) (using PYL for simplicity) and PP2C. However, PYL and PP2C protein family have many members, which have functional redundancy effect. Actually, ABA can regulate receptor protein to interact with many PP2C family members to activate multiple signaling pathways, which is one of the important reasons that ABA can enhance drought resistance of plant, but it can also influence many other physiological phenotype at the same time. Specific regulation of the interaction between PYL and PP2C can effectively solve the problem. So, how to design chemical probe for specific regulation of the dephosphorylation of PP2C and the related molecular mechanism is a major scientific issue. The techniques of computational chemistry, synthetic chemistry, chemical biology, biochemistry, and structural biology will be applied in this project. Finally, the chemical probes to specifically regulate the interaction between PYL and PP2C and the related molecular mechanism will be discovered through the research cycle of “computational simulation---probe design---interaction mechanism”. The implementation of this project will establish foundation for further developing efficient drought resistance regulator used in agriculture.