1-脱氧-D-木酮糖-5-磷酸还原异构酶(DXR),是新近被证实的具有筛选新型抗生素的潜在靶点。尽管磷酸类或者磷酸盐类化合物在分子水平上对DXR具有较好的抑制作用，但由于它们较高的亲水性，其在细胞水平和体内实验上的抑制作用并不理想。因此，如何在分子水平上获得具有较高活性的非磷酸类DXR抑制剂是当前DXR抑制剂研究的热点领域之一。.本项目旨在通过计算与实验相结合的方式获得具有强抑制作用的非磷酸类DXR抑制剂：基于当前最为前言的QM/MM计算方法，围绕着对DXR酶具有弱抑制作用的非磷酸类抑制剂(主要为中药提取物)，开展深入的分子机制研究以指导非磷酸类抑制剂的结构优化，从而获得一批潜在的具有强抑制作用的非磷酸类DXR抑制剂，并最终通过生物活性实验加以验证。

1-deoxy-D-xylulose 5-phosphate reductoisomerase(DXR), has emerged as an attractive target for the screening of novel antibiotic agents. The phosphoric acid or phosphate compounds have presented good inhibitory action on DXR at the molecular level, but due to their high hydrophilicity, their inhibitory effect on cell level and in vivo is not ideal. Therefore, it is one of the hot fields in the study of DXR inhibitors to obtain non-phosphate DXR inhibitors with high activity at the molecular level.. The final goal of this proposal is to obtain non-phosphate DXR inhibitors with strong inhibition by mean of combining the calculation and experiment: Based on the state-of-the-art QM/MM method, and surrounding the non-phosphate DXR inhibitors with weak inhibition (mainly for Chinese traditional medicine extracts) on DXR, launch the in-depth research of molecular mechanism to guide the structure optimization of the non-phosphate inhibitors, and thus gain a number of potential non-phosphate inhibitors with strong inhibitory effect on DXR, and finally verified through biological activity test.