利用计算机模拟筛选可特异性结合并抑制FtsZ聚合的小分子化合物

COMPUTER-AIDED VIRTUAL SCREENING OF FTSZ FOR NOVEL INHIBITORS

FtsZ(丝状温度敏感蛋白Z)是微管蛋白在原核生物中的同源物,在细胞分裂过程中起着关键作用.利用枯草芽孢杆菌的FtsZ晶体结构,针对其GTPase位点,对8万个小分子进行了虚拟筛选,结果发现了7个可以结合到GTPase口袋中的小分子化合物.依据预测的结合模式,这些小分子可以分为2组.其中组1基本上完全占据了GTP/GDP的结合位置,与GTP的嘌呤结合口袋附近的疏水氨基酸F136、F183、L190可能具有相互作用.而组2的小分子所占据的结合位置则与GTP/GDP有明显区别.本工作预测的小分子化合物可以成为潜在的抑制剂,以它们作为起点,我们下一步将通过生化试验检测其抑制效果,从而为开发抑制剂提供基础.

FtsZ （filamentation temperature-sensitive mutant Z） is a prokaryotic tubulin homolog essential for cell division in bacteria. In this study, a virtual screening study on GTPase pocket of Bacillus subtilis FtsZ crystal structure was performed. Having screened a library of 80 000 small molecule compounds, 7 compounds were predicted to bind FtsZ. These compounds were grouped into two classes. Class 1 occupied GTP/GDP binding region and formed hydrophobic interactions with residues F136, F183 and L190 around purine binding pocket. Binding sites for class 2 compounds, however, only partially overlapped with GTP/GDP. Compoundsdiscovered in this study will be validated. They may become a starting point for developing new anti-bacteria drugs.