Singh Gagandeep, Hossain Md Alamgir, Al-Fahad Dhurgham, Gupta Vandana, Tandon Smriti, Soni Hemant, Narasimhaji Cheemalapati Venkata, Jaremko Mariusz, Emwas Abdul-Hamid, Anwar Md Jamir, Azam Faizul
Section of Microbiology, Central Ayurveda Research Institute, Jhansi, Uttar Pradesh, India, 284003.
Kusuma School of Biological Sciences, Indian Institute of Technology Delhi, New Delhi, India, 110016.
Biochem Biophys Rep. 2024 Oct 21;40:101854. doi: 10.1016/j.bbrep.2024.101854. eCollection 2024 Dec.
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.
在过去十年中，细菌对抗生素的耐药性以及耐多药细菌感染的患者数量显著增加。本研究采用计算方法从野生蘑菇中鉴定潜在的抗菌化合物。将野生蘑菇产生的26种已知化合物进行对接，以评估它们与抗生素药物靶点如青霉素结合蛋白-1a（PBP1a）、DNA旋转酶和异亮氨酰-tRNA合成酶（ILERS）的亲和力。通过基于多受体构象（MRC）的对接研究进一步验证对接分数。基于MRC的对接结果，筛选出八个分子进行ADMET分析。进一步进行分子动力学（MD）模拟以评估配体-蛋白质复合物的构象稳定性。通过gmx_MMPBSA方法计算结合能。数据以均方根偏差和均方根波动表示，证明了奥氏皮质黄质A、奥氏皮质红素和融合菌素在生理条件下与几种蛋白质形成复合物时的稳定性。其中，与各自的参考配体相比，奥氏皮质黄质A与PBP1a和ILERS表现出更好的结合亲和力。本研究是初步的，旨在利用野生蘑菇产生的天然化合物，推动寻找有能力克服常见细菌抗微生物耐药性的化合物。需要进一步的实验验证来证明所研究化合物的临床应用合理性。
