社区和医院中尿路感染（UTI）中多药耐药病原体的增加威胁着我们治疗这些常见病原体的能力。尿路致病性大肠杆菌（UPEC）菌株是与尿路感染发展有关的最常见的尿路病变。这项工作旨在通过从公共数据库中虚拟筛选小分子来引入生物活性天然产物，以通过抑制FimH来防止生物膜的形成。在UPEC致病性中起关键作用的1型菌毛。通过分子对接对来自NPASS数据库的总共30926个小分子进行筛选。随后进行模拟ADME研究，七个分子显示出-6.8至-8.7kcal/mol范围内的有希望的对接结果。作为对接得分发现的结果，进行100ns分子动力学(MD)模拟。基于MM-PBSA分析，NPC313334配体在分子动力学模拟过程中与FimH蛋白的结合口袋显示出高结合亲和力-42和稳定性。还对配体进行DFT计算以计算化合物的HOMO-LUMO能量,以便了解它们的结构和反应性。这项研究表明，NPC313334可能是一种可能的抗菌药物候选药物，其靶向FimH以减少UPEC相关尿路感染的数量。由RamaswamyH.Sarma沟通。
The increase in multidrug-resistant pathogens in urinary tract infections (UTIs) among communities and hospitals threatens our ability to treat these common pathogens. Uropathogenic Escherichia coli (UPEC) strains are the most frequent uropathies linked to the development of UTIs. This work aims to introduce bioactive natural products via virtual screening of small molecules from a public database to prevent biofilm formation by inhibiting FimH, a type 1 fimbriae that plays a crucial role in UPEC pathogenicity. A total of 30926 small molecules from the NPASS database were subjected to screening via molecular docking. Followed by performing in silico ADME studies, seven molecules showed promising docking results ranging from -6.8 to -8.7 kcal/mol. As a result of the docking score findings, 100 ns Molecular dynamics (MD) simulations were performed. Based on MM-PBSA analysis, NPC313334 ligand showed high binding affinity -42 and stability with the binding pocket of FimH protein during molecular dynamic simulations. DFT calculations were also performed on the ligands to calculate the HOMO-LUMO energies of the compounds in order to an idea about their structure and reactivity. This research suggests that NPC313334 may be a possible antibacterial drug candidate that targets FimH to reduce the number of UPEC-related urinary tract infections.Communicated by Ramaswamy H. Sarma.
