An in-silico approach to target multiple proteins involved in anti-microbial resistance using natural compounds produced by wild mushrooms

IF 2.3 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemistry and Biophysics Reports Pub Date : 2024-10-21 DOI:10.1016/j.bbrep.2024.101854
Gagandeep Singh , Md Alamgir Hossain , Dhurgham Al-Fahad , Vandana Gupta , Smriti Tandon , Hemant Soni , Cheemalapati Venkata Narasimhaji , Mariusz Jaremko , Abdul-Hamid Emwas , Md Jamir Anwar , Faizul Azam
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Abstract

Bacterial resistance to antibiotics and the number of patients infected by multi-drug-resistant bacteria have increased significantly over the past decade. This study follows a computational approach to identify potential antibacterial compounds from wild mushrooms. Twenty-six known compounds produced by wild mushrooms were docked to assess their affinity with drug targets of antibiotics such as penicillin-binding protein-1a (PBP1a), DNA gyrase, and isoleucyl-tRNA synthetase (ILERS). Docking scores were further validated by multiple receptor conformer (MRC)-based docking studies. Based on the MRC-based docking results, eight molecules were shortlisted for ADMET analysis. Molecular dynamics (MD) simulations were further performed to evaluate the conformational stability of the ligand-protein complexes. Binding energies were computed by the gmx_MMPBSA method. The data were obtained in terms of root-mean square deviation, and root-mean square fluctuation justified the stability of Austrocortilutein A, Austrocortirubin, and Confluentin in complex with several proteins under physiological conditions. Among these, Austrocortilutein A displayed better binding affinity with PBP1a and ILERS when compared with their respective reference ligands. This study is preliminary and aims to help drive the search for compounds that have the capacity to overcome the anti-microbial resistance of prevalent bacteria, using natural compounds produced by wild mushrooms. Further experimental validation is required to justify the clinical use of the studied compounds.

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利用野生蘑菇产生的天然化合物靶向涉及抗微生物抗药性的多种蛋白质的硅内方法
在过去十年中,细菌对抗生素的耐药性和感染多重耐药菌的患者人数大幅增加。本研究采用计算方法从野生蘑菇中找出潜在的抗菌化合物。研究人员对野生蘑菇产生的 26 种已知化合物进行了对接,以评估它们与青霉素结合蛋白-1a (PBP1a)、DNA 回旋酶和异亮氨酰-tRNA 合成酶 (ILERS) 等抗生素药物靶标的亲和力。基于多重受体构象(MRC)的对接研究进一步验证了对接得分。根据基于 MRC 的对接结果,筛选出 8 个分子进行 ADMET 分析。为评估配体-蛋白质复合物的构象稳定性,进一步进行了分子动力学(MD)模拟。结合能由 gmx_MMPBSA 方法计算得出。得到的均方根偏差和均方根波动数据证明了奥曲肽肽 A、奥曲肽和 Confluentin 在生理条件下与几种蛋白质复合物的稳定性。其中,奥曲肽 A 与 PBP1a 和 ILERS 的结合亲和力优于各自的参考配体。这项研究是初步性的,目的是利用野生蘑菇产生的天然化合物,帮助寻找有能力克服流行细菌抗微生物耐药性的化合物。要证明所研究化合物的临床用途,还需要进一步的实验验证。
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来源期刊
Biochemistry and Biophysics Reports
Biochemistry and Biophysics Reports Biochemistry, Genetics and Molecular Biology-Biophysics
CiteScore
4.60
自引率
0.00%
发文量
191
审稿时长
59 days
期刊介绍: Open access, online only, peer-reviewed international journal in the Life Sciences, established in 2014 Biochemistry and Biophysics Reports (BB Reports) publishes original research in all aspects of Biochemistry, Biophysics and related areas like Molecular and Cell Biology. BB Reports welcomes solid though more preliminary, descriptive and small scale results if they have the potential to stimulate and/or contribute to future research, leading to new insights or hypothesis. Primary criteria for acceptance is that the work is original, scientifically and technically sound and provides valuable knowledge to life sciences research. We strongly believe all results deserve to be published and documented for the advancement of science. BB Reports specifically appreciates receiving reports on: Negative results, Replication studies, Reanalysis of previous datasets.
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