针对幽门螺旋杆菌的外排泵抑制剂的虚拟筛选、对接和分子动力学研究

IF 2.2 4区 化学 Q2 Engineering Chemical Papers Pub Date : 2024-10-07 DOI:10.1007/s11696-024-03719-5
B. Akshaya Devi, Dhananjay Jade, K. H Sreenithya, Michael A. Harrison, Shobana Sugumar
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引用次数: 0

摘要

幽门螺旋杆菌是一种革兰氏阴性细菌,可感染人类胃肠道粘膜,是一种重要的人类病原体,影响着全球 50%的人口。MATE蛋白家族中的多药外排泵mepA是幽门螺旋杆菌中一个潜在的外排泵靶点,它将多种药物排出幽门螺旋杆菌之外,由417个氨基酸组成。本研究采用分子对接、药物相似性评估、密度泛函理论[DFT]、分子动力学(MD)模拟和自由能计算等方法,分析植物化学物质与mepA蛋白之间的相互作用,旨在确定幽门螺旋杆菌中多药外排泵mepA的潜在抑制剂。研究人员从数据库中筛选出了与 mepA 蛋白结合亲和力最高的化合物。总之,这项研究从 30 个基于结合亲和力得分的顶级化合物中发现了三个有潜力的天然化合物桧黄酮(- 10.9 kcal/mol)、伊泊明(- 10.7 kcal/mol)和羽扇豆异黄酮 M(- 10.5 kcal/mol),它们通过分子对接显示出与 mepA 的显著结合亲和力,表明它们具有阻断外排泵和增强抗生素作用的潜力,有可能抑制幽门螺旋杆菌中的多药外排泵 mepA。此外,我们还选择了 3 种化合物中的一种复合物进行 DFT 分析,并通过分子动力学模拟计算了蛋白质和蛋白质配体复合物的稳定性,同时还计算了所选羽扇豆异黄酮 M 复合物蛋白质的结合自由能(- 98.948 kJ/mol)。这项研究强调了所选化合物抑制 mepA 外排泵的能力,为开发针对耐多药病原体的新型治疗策略铺平了道路。
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Virtual screening, docking, molecular dynamics study of efflux pump inhibitors against Helicobacter pylori

Helicobacter pylori is a Gram-negative bacterium that infects the human gastrointestinal mucosa and is a significant human pathogen, affecting 50% of the world’s population. Multidrug Efflux Pump mepA from the MATE family of proteins acts as a potential efflux pump target in Helicobacter pylori which exports multiple drugs outside the Helicobacter pylori and consists of 417 amino acids. This study aimed to identify potential inhibitors of the multidrug efflux pump mepA in Helicobacter pylori using in-silico approaches that employed molecular docking, drug-likeness evaluation, density functional theory [DFT], molecular dynamics (MD) simulations, and free energy calculations to analyze, the interactions between phytochemicals compounds and mepA protein. The best compounds exhibiting the highest binding affinities toward mepA were selected among all the screened phytochemical compounds from the database. Overall, this research identified three promising natural compounds Hinokiflavone (− 10.9 kcal/mol), Ipomine (− 10.7 kcal/mol), and Lupinisoflavone M (− 10.5 kcal/mol) from 30 top compounds based on binding affinity score, which demonstrated remarkable binding affinities toward mepA through molecular docking, suggesting their potential to block the efflux pump and potentiate antibiotic action with the potential to inhibit the multidrug efflux pump mepA in Helicobacter pylori. Besides, we select one complex for 3 compounds for an analysis of DFT and calculate the stability of protein and protein–ligand complex by Molecular Dynamics simulation along with this we calculate the binding free energy for the complex’s protein for selected Lupinisoflavone M complex (− 98.948 kJ/mol). The study highlights the promising capacity of the selected compounds to inhibit the mepA efflux pump, potentially paving the way for developing novel therapeutic strategies against multidrug-resistant pathogens.

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来源期刊
Chemical Papers
Chemical Papers Chemical Engineering-General Chemical Engineering
CiteScore
3.30
自引率
4.50%
发文量
590
期刊介绍: Chemical Papers is a peer-reviewed, international journal devoted to basic and applied chemical research. It has a broad scope covering the chemical sciences, but favors interdisciplinary research and studies that bring chemistry together with other disciplines.
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