Department of Biotechnology, PES University, Bengaluru, India.
Department of Biotechnology, Siddaganga Institute of Technology, Tumakuru, India.
J Biomol Struct Dyn. 2024 Apr;42(6):3030-3050. doi: 10.1080/07391102.2023.2212060. Epub 2023 May 18.
Incidences of Methicillin-Resistant and Multi-Drug Resistant causing skin and soft tissue infections are becoming more prevalent due to repeated mutations and changes in the environment. a well-known Indian herbal medicinal plant, is shown to have antioxidant, antibacterial, and anti-inflammatory activity. This comparative study focuses on the molecular docking (PyRx v0.9.8) of ligand binding domains of WbpE Aminotransferase involved in O-antigen assembly in (3NU7) and Beta-Lactamase found in (1BLC) with selected phytocompounds of along with a known binder and a clinical reference drug. This was followed by molecular dynamics simulation studies (GROMACS v2019.4) for the docked complexes (with Geranyl acetate) with the best binding affinities (-23.4304 kJ/mol with Beta-Lactamase and -28.4512 kJ/mol with WbpE Aminotransferase) and maximum hydrogen bonds. Molecular dynamics simulation studies for both the proteins demonstrated that the complex with Geranyl acetate showed stability comparable to the complex with reference drug observed Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF) and H-bond analyses. Changes in the secondary structural elements indicated that Geranyl acetate could possibly cause improper functioning of WbpE Aminotransferase leading to disrupted cell wall formation. Further, MM/PBSA analyses showed significant binding affinity of Geranyl acetate with WbpE Aminotransferase and Beta-Lactamase. This study aims to provide rationale for further studies of as an antimicrobial, and to contextualise the results in the current scenario of growing antimicrobial resistance. HIGHLIGHTSPhytoconstituents present in show significant binding affinity to the proteins in and Geranyl acetate exhibited the highest binding affinity with WbpE Aminotransferase involved in O-antigen assembly in (PDB ID:3NU7) and Beta-Lactamase found in (PDB ID: 1BLC)Molecular dynamics simulation analyses show that the phytoconstituent, Geranyl acetate has an effect similar to the clinical reference drug, thus exhibiting potential antibacterial activity.Communicated by Ramaswamy H. Sarma.
由于环境的反复突变和变化，耐甲氧西林金黄色葡萄球菌和多药耐药金黄色葡萄球菌引起的皮肤和软组织感染的发病率越来越高。一种著名的印度草药植物，被证明具有抗氧化、抗菌和抗炎活性。本比较研究侧重于配体结合域的分子对接（PyRx v0.9.8），涉及参与 O-抗原组装的 WbpE 氨基转移酶（在 3NU7 中）和在 1BLC 中发现的β-内酰胺酶，与 中的选定植物化合物以及已知结合物和临床参考药物一起。随后，对具有最佳结合亲和力（与β-内酰胺酶为-23.4304 kJ/mol，与 WbpE 氨基转移酶为-28.4512 kJ/mol）和最大氢键的对接复合物（与乙酸香叶酯）进行了分子动力学模拟研究（GROMACS v2019.4）。对两种蛋白质的分子动力学模拟研究表明，与乙酸香叶酯的复合物表现出与观察到的参考药物复合物相当的稳定性 根均方偏差（RMSD）、根均方波动（RMSF）和氢键分析。二级结构元素的变化表明，乙酸香叶酯可能导致 WbpE 氨基转移酶功能异常，从而破坏细胞壁形成。此外，MM/PBSA 分析表明乙酸香叶酯与 WbpE 氨基转移酶和β-内酰胺酶具有显著的结合亲和力。本研究旨在为进一步研究作为一种抗菌剂提供依据，并在当前抗菌药物耐药性日益增长的背景下对结果进行背景化。 要点植物成分在 中表现出与 中蛋白质的显著结合亲和力，乙酸香叶酯与参与 中 O-抗原组装的 WbpE 氨基转移酶（PDB ID：3NU7）和 中发现的β-内酰胺酶（PDB ID：1BLC）表现出最高的结合亲和力。分子动力学模拟分析表明，植物成分乙酸香叶酯对临床参考药物具有类似的作用，因此表现出潜在的抗菌活性。由 Ramaswamy H. Sarma 传达。
