甲硫氨酰 - tRNA合成酶抑制剂的三维定量构效关系研究与分子对接
3-D-QSAR study and molecular docking of methionyl-tRNA synthetase inhibitors.
作者信息
Kim Su Yeon, Lee Jeewoo
机构信息
Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim-Dong, Kwanak-Ku, Seoul 151-742, South Korea.
出版信息
Bioorg Med Chem. 2003 Dec 1;11(24):5325-31. doi: 10.1016/j.bmc.2003.09.044.
The three-dimensional quantitative structure-activity relationships of 57 2-[(aminopropyl)amino]-4(1H)-quinolinone analogues as Staphylococcus aureus methionyl-tRNA synthetase (MetRS) inhibitors with excellent antibacterial profile were investigated and docking studies were performed. The CoMFA analysis provided a model with a q(2) value of 0.579 and an r(2) value of 0.970, in which the good correlation between the MetRS inhibitory activities (IC(50)) and the steric and electrostatic molecular fields around the analogues was examined. Two inhibitors (1 and 17) were docked into the binding pocket of Escherichia coli MetRS imported from the X-ray crystal structure of the MetRS-methionine complex, and the details of their interaction with the amino acids of the active site are discussed.
研究了57种具有优异抗菌谱的2-[(氨丙基)氨基]-4(1H)-喹啉酮类似物作为金黄色葡萄球菌甲硫氨酰-tRNA合成酶（MetRS）抑制剂的三维定量构效关系，并进行了对接研究。比较分子场分析（CoMFA）提供了一个模型，其q(2)值为0.579，r(2)值为0.970，其中研究了MetRS抑制活性（IC(50)）与类似物周围的空间和静电分子场之间的良好相关性。将两种抑制剂（1和17）对接至从MetRS-甲硫氨酸复合物的X射线晶体结构导入的大肠杆菌MetRS的结合口袋中，并讨论了它们与活性位点氨基酸相互作用的细节。
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