Computational Biology and Molecular Simulations Laboratory, Department of Biophysics, School of Medicine, Bahcesehir University, Istanbul, Turkey; Neuroscience Program, Graduate School of Health Sciences, Bahcesehir University, Istanbul, Turkey.
College of Informatics, Huazhong Agricultural University (HZAU), Wuhan, China.
J Mol Graph Model. 2018 Oct;85:122-129. doi: 10.1016/j.jmgm.2018.07.010. Epub 2018 Jul 27.
Appropriate therapeutic solutions against Staphylococcal infections are currently limited. To work out the complex task of challenging drug resistance in Staphylococcus aureus, new compounds with novel modes of action are required. In this study, we performed target-driven virtual screening to filter exhaustive phytochemical libraries that can inhibit the activity of S. aureus DNA Gyrase B (Gyr B). Three top-ranked hit molecules (Mangostenone E, Candenatenin A and 2,4,4'-trihydroxydihydrochalcone) were identified from comprehensive molecular docking studies based on their strong spatial affinity with key catalytic residues of the binding pocket of DNA GyrB, especially with the well-known crucial residue Asp81. Molecular dynamics (MD) simulations were performed for these identified hit molecules for better understanding of their dynamical and structural profiles throughout the MD simulations. These compounds can be explored as future lead optimization molecules to discover a new class of antibiotics against resistant Staphylococcus aureus strains.
目前针对葡萄球菌感染的治疗方法有限。为了解决金黄色葡萄球菌耐药性这一复杂问题，需要寻找具有新型作用机制的新化合物。在这项研究中，我们进行了基于靶点的虚拟筛选，以筛选能够抑制金黄色葡萄球菌 DNA 回旋酶 B（Gyr B）活性的 exhaustive 植物化学文库。通过基于关键催化残基结合口袋的 DNA GyrB 的综合分子对接研究，我们从全面的分子对接研究中鉴定出三个排名靠前的命中分子（Mangostenone E、Candenatenin A 和 2,4,4'-三羟基二氢查尔酮），特别是与众所周知的关键残基 Asp81 具有很强的空间亲和力。对这些鉴定出的命中分子进行分子动力学（MD）模拟，以更好地了解它们在整个 MD 模拟过程中的动态和结构特征。这些化合物可以作为未来的先导优化分子进行探索，以发现针对耐药金黄色葡萄球菌菌株的新型抗生素。
