The First Clinical College, Guangdong Medical University, Zhanjiang 524023, China.
The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, China.
Molecules. 2021 Oct 25;26(21):6426. doi: 10.3390/molecules26216426.
is an opportunistic pathogen that can cause fatal bacterial infections. MurD catalyzes the formation of peptide bond between UDP--acetylehyl-l-alanine and d-glutamic acid, which plays an important role in the synthesis of peptidoglycan and the formation of cell wall by . Because is resistant to most existing antibiotics, it is necessary to develop new inhibitors. In this study, Schrodinger 11.5 Prime homology modeling was selected to prepare the protein model of MurD enzyme, and its structure was optimized. We used a virtual screening program and similarity screening to screen 47163 compounds from three marine natural product libraries to explore new inhibitors of . ADME provides analysis of the physicochemical properties of the best performing compounds during the screening process. To determine the stability of the docking effect, a 100 ns molecular dynamics was performed to verify how tightly the compound was bound to the protein. By docking analysis and molecular dynamics analysis, both 46604 and 46608 have strong interaction with the docking pocket, have good pharmacological properties, and maintain stable conformation with the target protein, so they have a chance to become drugs for . Through virtual screening, similarity screening, ADME study and molecular dynamics simulation, 46604 and 46608 were selected as potential drug candidates for .
是一种机会性病原体，可以导致致命的细菌感染。MurD 酶催化 UDP--乙酰-l-丙氨酸和 d-谷氨酸之间肽键的形成，在肽聚糖的合成和细胞壁的形成中发挥重要作用。由于 对大多数现有抗生素具有耐药性，因此有必要开发新的抑制剂。在这项研究中，选择了 Schrödinger 11.5 Prime 同源建模来制备 MurD 酶的蛋白质模型，并对其结构进行了优化。我们使用虚拟筛选程序和相似性筛选从三个海洋天然产物库中筛选了 47163 种化合物，以探索 的新抑制剂。ADME 在筛选过程中提供了最佳表现化合物的物理化学性质分析。为了确定对接效果的稳定性，进行了 100ns 的分子动力学模拟，以验证化合物与蛋白质的结合紧密程度。通过对接分析和分子动力学分析，46604 和 46608 与对接口袋都具有很强的相互作用，具有良好的药理学性质，并且与靶蛋白保持稳定的构象，因此它们有机会成为 的药物。通过虚拟筛选、相似性筛选、ADME 研究和分子动力学模拟，选择了 46604 和 46608 作为 的潜在药物候选物。
