本项目基于化学信息学和生物信息学技术，综合运用结构生物学、网络药理学、计算机辅助药物设计学等多种技术手段，挖掘Nrf2-Keap1"蛋白-蛋白"相互作用过程中的作用信息和模式特征，阐明"蛋白-蛋白"相互作用过程的科学内涵，建立高效准确的研究新方法和新技术，从天然产物中发现能够满足Nrf2-Keap1相互作用特征的新型天然产物优势骨架，设计和合成具有模拟"蛋白-蛋白"相互调控作用的类天然产物化合物库，实现药物分子设计的源头创新。在本项目中，我们将构建①发现"蛋白-蛋白"相互作用结合热区的快速高效的新方法；②基于"蛋白-蛋白"相互作用动态过程关键热区的研究体系和方法；③设计具有高度靶标适配性及良好成药性的类天然产物数据库体系；④建立近似功能、彼此关联的靶标群落和网络药理学新模型。通过这些新技术和方法建立高效率、低成本、可靠度高、适用性广的"蛋白-蛋白"相互作用调控剂研究的研究体系。

In this application, cheminformatics and bioinformatics techniques, accompanied with structure biology, network pharmacology, and computer-aided drug design, will be applied as the basic methodology for deeply clarifying the Nrf2-Keap1 "protein-protein" interaction system. The binding mode of the Nrf2-Keap1 interaction pattern as well as the key information will be fully described. High efficient and precise research new methods will be constructed for the identification of novel scaffold from natural products and their derivatives that can fulfill the binding interaction characters. Rational molecular design on the basis of the cheminformatics and bioinformatics will be fully emphasized to generate natural-products-like compound databases. In this application, we will set up 1) new method for the high efficiently recognization of hot spot in the "protein-protein" interaction system; 2) novel research skills and schemes for the hot spot on the basis of their dynamic processes; 3) natural product and natural-products-like compound databases that can fulfill the characters of "protein-protein" interaction system and possess well drug-like properties; 4) novel target network on the basis of different "protein-protein" interaction systems. With the help of these novel skills and methodologies, we will construct high effcient, low cost, reliabile and common research systems for the design of new modulators for "protein-protein" interaction system.