Dr. D. Y. Patil Vidyapeeth, Bioinformatics Research Laboratory, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Pune, India.
Dr. D. Y. Patil Vidyapeeth, Microbial Diversity Research Centre, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Pune, India.
J Biomol Struct Dyn. 2023 Apr;41(7):2698-2712. doi: 10.1080/07391102.2022.2038271. Epub 2022 Feb 14.
is a notorious multidrug resistant bacterium responsible for several hospital acquired infections assisted by its capacity to develop biofilms. BfmR (RstA), a response regulator from the BfmR/S two-component signal transduction system, is the major controller of biofilm development and formation. As a result, BfmR represents a novel target for anti-biofilm treatment against . The discovery of the high-resolution crystal structure of BfmR provides a good chance for computational screening of its probable inhibitors. Therefore, in this study we aim to search new, less toxic, and natural BfmR inhibitors from 8450 phytomolecules available in the Indian Medicinal Plants, Phytochemistry and Therapeutic (IMPPAT) database by analyzing molecular docking against BfmR (PDB ID: 6BR7). Out of these 8450 phytomolecules 6742 molecules were successfully docked with BfmR with the docking score range -6.305 kcal/mol to +5.120 kcal/mol. Structure based-molecular docking (SB-MD) and ADMET (absorption, distribution, metabolism, excretion, & toxicity) profile examination revealed that Norepinephrine, Australine, Calystegine B3, 7,7 A-Diepialexine, and Alpha-Methylnoradrenaline phytocompounds strongly binds to the active site residues of BfmR. Furthermore, molecular dynamics simulation (MDS) studies for 100 ns and the binding free energy (MM/GBSA) analysis elucidated the binding mechanism of Calystegine B3, 7,7 A-Diepialexine, and Alpha-Methylnoradrenaline to BfmR. In summary, these phytocompounds seems to have the promising molecules against BfmR, and thus necessitates further verification by both and experiments. HighlightsBfmR plays a key role in biofilm development and exopolysaccharide (EPS) synthesis in Computational approach to search for promising BfmR inhibitors from IMPAAT database.The lead phytomolecules such as Calystegine B3, 7,7 A-Diepialexine, and Alpha-Methylnoradrenaline displayed significant binding with BfmR active site.The outcome of BfmR binding phytomolecules has broadened the scope of hit molecules validation.Communicated by Ramaswamy H. Sarma.
是一种臭名昭著的多药耐药菌，它能够形成生物膜，从而导致多种医院获得性感染。BfmR（RstA）是 BfmR/S 双组分信号转导系统的一种反应调节剂，是生物膜发育和形成的主要控制器。因此，BfmR 代表了针对 的新型抗生物膜治疗靶标。BfmR 的高分辨率晶体结构的发现为计算筛选其可能的抑制剂提供了很好的机会。因此，在这项研究中，我们旨在通过分析与 BfmR（PDB ID：6BR7）的分子对接，从印度药用植物、植物化学和治疗学 (IMPPAT) 数据库中的 8450 种植物分子中搜索新型、低毒、天然的 BfmR 抑制剂。在这 8450 种植物分子中，有 6742 种分子成功与 BfmR 对接，对接评分范围为-6.305 kcal/mol 至+5.120 kcal/mol。基于结构的分子对接 (SB-MD) 和 ADMET（吸收、分布、代谢、排泄和毒性）谱分析表明，去甲肾上腺素、澳洲茄碱、长春碱 B3、7,7A-二表阿立必利、α-甲基去甲肾上腺素等植物化合物与 BfmR 的活性位点残基强烈结合。此外，100 ns 的分子动力学模拟 (MDS) 研究和结合自由能 (MM/GBSA) 分析阐明了长春碱 B3、7,7A-二表阿立必利和 α-甲基去甲肾上腺素与 BfmR 的结合机制。总之，这些植物化合物似乎是针对 BfmR 的有前途的分子，因此需要通过 和 实验进一步验证。
