高效性、选择性以及规避抗药性（或反抗性）是生态农药分子设计所面临的关键科学问题。以往的农药分子设计往往只偏重于解决农药分子的高效性和选择性，而忽略了规避抗药性（或反抗性）。如何在解决高效性和选择性的同时，使农药分子能有效规避抗药性（或反抗性）是农药分子设计所面临的一个重大挑战。本项目针对有害生物多样性、农药防治对象多样性和保护对象多样性的特点，拟采用比较化学生物学方法，从基因和种属两个层面上深入开展不同种属农药靶标产生抗药性的分子机制，进一步发展和完善靶标分子抗性及选择性的预测方法学，挖掘低抗性风险的作用靶位，寻找全新农药作用机制，建立和发展基于靶标组结构的分子设计方法，指导设计合成综合高效性、选择性和规避抗药性（或反抗性）的新型生态农药分子，力争创制出1~2个具有开发前景的候选生态农药。本项目的实施将进一步丰富和完善我国农药创新研究体系，提升我国农药创制的国际影响力。

High potency, selectivity and anti-resistance are three key scientific problems that molecular design of ecological pesticide is facing. Traditional molecular design always focused on the high potency and selectivity of pesticide molecules, while ignoring the anti-resistance. Therefore, it is a big challenge how to solve the high potency, selectivity and anti-resistance at the same time. Keep in mind that pest diversity, pesticide control object diversity and protection of diversity of characteristics, the method of comparative chemical biology will be applied to understand the molecular mechanism of resistance associated with different action targets from different species at the levels of gene and species. At the same time, this project is aimed to develop new methods for target resistance prediction, to mine target site with low risk of resistance, and to look for new action mechanism. Finally, this project is also aimed to develop a new molecular design method, called targetome structure-based design (TSBD), to guide the molecular design of new pesticide with high potency, selectivity and low risk of resistance. We believe that this project will contribute significantly to the basic research of pesticide in China, and further enhance the international influence of pesticide research and development in China.