作用于植物细菌群体感应信号分子的受体LuxR的化学抑制剂的合理设计

项目名称： 作用于植物细菌群体感应信号分子的受体LuxR的化学抑制剂的合理设计

项目编号： No.31272075

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 农业科学

项目作者： 董燕红

作者单位： 中国农业大学

项目金额： 75万元

中文摘要： 群体感应(QS)广泛存在于细菌中，是细菌根据细胞密度变化调控基因表达的一种机制。许多植物病原菌依赖QS调控致病基因和毒性因子的表达，导致植物发病。本项目选择QS系统的信号分子受体蛋白LuxR为研究对象，通过LuxR的晶体结构，利用分子对接和分子动力学等方法模拟抑制分子与受体在不同环境下的结合过程，探讨小分子与受体的作用机理，建立合理的预测模型，进行虚拟筛选和基于LuxR的合理设计与合成，最终通过生物学活性评价，发现具有潜在应用前景的抑制QS系统候选化合物。本项目研究将为控制植物细菌病害提供了一种有效的新方法，为基于靶标受体的新农药创制提供重要的理论指导。

中文关键词： 群体感应；信号分子受体；抑制剂；分子设计；合成

英文摘要： Quorum-sensing (QS), which regulates gene expression depending on population density, is universal in bacteria. QS is involved in the regulation of virulent factor and pathogenic gene expression, and plays a key role in causing plant disease by plant bacterial pathogens. The project choose recptor protein LuxR in QS system as reaserch object, through crystal structure of LuxR, the binding process of the inhibitors to receptor in diffierent environment will be simulated. After using molecular docking and dynamics, the mechanism of small molecules to receptor will be studied and reasonable forecasting model will be built up. Then virtual screening and rational design and synthesis based on LuxR will be carried out. Finally, the inhibitor candidate compounds with potential application are discovered by bioactivity evaluation. The project will provide a promising approach for controlling plant disease caused by QS-mediated bacterial pathogens, and important basis for novel pesticides discovery based on target receptor.

英文关键词： Quorum Sensing；Signal Receptor；Inhibitors；Design；synthesis