State Key Laboratory of Chemical Biology and Drug Discovery, and Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong, China.
Department of Microbiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
Int J Mol Sci. 2022 Apr 7;23(8):4085. doi: 10.3390/ijms23084085.
are a family of bacterial species significantly affecting human health. In addition, environmental represent one of the major causes of diverse livestock diseases. Due to antimicrobial resistance, there is an urgent need for novel antimicrobial agent discovery against . We discovered a class of benzoic acid derivatives named sigmacidins inhibiting the bacterial RNA polymerase-σ factor interaction and demonstrating excellent antimicrobial activity against . In this work, a combinational computer approach was applied to gain insight into the structural basis and mechanism of action of sigmacidins as antimicrobials against . Both two- and three-dimensional quantitative structure-active relationships (2D and 3D QSAR) of sigmacidins displayed good predictive ability. Moreover, molecular docking and molecular dynamics simulation studies disclosed possible contacts between the inhibitors and the protein. The results obtained in this study provided understanding and new directions to the further optimizations of sigmacidins as novel antimicrobials.
是一类对人类健康有重大影响的细菌物种。此外，环境代表了多种家畜疾病的主要原因之一。由于抗菌药物耐药性的存在，迫切需要发现针对的新型抗菌药物。我们发现了一类名为 sigma 菌素的苯甲酸衍生物，它能抑制细菌 RNA 聚合酶-σ 因子相互作用，并对表现出优异的抗菌活性。在这项工作中，应用了一种组合计算机方法来深入了解 sigma 菌素作为抗菌药物对抗的结构基础和作用机制。sigma 菌素的二维和三维定量构效关系（2D 和 3D QSAR）都显示出良好的预测能力。此外，分子对接和分子动力学模拟研究揭示了抑制剂与蛋白质之间可能的相互作用。本研究的结果为进一步优化 sigma 菌素作为新型抗菌药物提供了理解和新的方向。
