用于控制硫酸盐还原菌的异化亚硫酸盐还原酶抑制剂的虚拟筛选和分子动力学模拟
Virtual screening and molecular dynamic simulations of dissimilatory sulfite reductase inhibitors for the control of sulphate reducing bacteria.
作者信息
Oyewole Oluwafemi Adebayo, Adamu Rahma Muhammad, Saidu Umar, Cosa Sekelwa, Simelane Mthokozisi B C, Rahman Md Atiar, Ibrahim Mohammed Auwal
机构信息
Department of Microbiology, Federal University of Technology, Minna, Nigeria.
Department of Plant Biology, Federal University, Dutse, Nigeria.
出版信息
In Silico Pharmacol. 2025 Jun 17;13(2):90. doi: 10.1007/s40203-025-00367-9. eCollection 2025.
UNLABELLED
Dissimilatory sulfite reductase (DSR) plays a crucial role in the metabolism of sulfate-reducing bacteria (SRB), which contribute to environmental hazards such as biocorrosion and sulfide pollution. The search for effective DSR inhibitors has been challenging due to the difficulty in culturing strict anaerobes. In this study, we employed molecular docking and 100 ns molecular dynamics (MD) simulations to screen 248 microbially-derived compounds for their potential as DSR inhibitors. Based on docking scores, nine hit compounds were identified, with dehydrocitreaglycon A exhibiting the highest binding affinity (-9.4 kcal/mol), followed by citreamicin theta A and etamycin. Hydrogen bond interaction analysis revealed that key active site residues, including Arg83, Arg101, and Lys215, played significant roles in ligand binding. MD simulations revealed varying stability among the DSR-compound complexes, with arisugacin A demonstrating the highest stability and minimal fluctuations, while antimycin A1 and peniciadametizine A showed the highest instability. The principal component analysis (PCA) indicated greater conformational flexibility in complexes with antimycin A1, etamycin, citreamicin theta A, and terretonin G. Binding free energy calculations confirmed that dehydrocitreaglycon A (-112.13 kJ/mol) and strobilurin (-107.66 kJ/mol) had the most favorable interactions with DSR. Furthermore, an in silico environmental toxicity assessment indicated that some compounds, such as salmochelin sx, posed higher toxicity risks, whereas others, like dehydrocitreaglycon A, showed lower environmental impact. Overall, our findings highlight strobilurin, arisugacin A, and dehydrocitreaglycon A as promising DSR inhibitors, warranting further investigation for potential applications in SRB control.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40203-025-00367-9.
未标记
异化亚硫酸盐还原酶（DSR）在硫酸盐还原菌（SRB）的代谢中起着关键作用，而硫酸盐还原菌会导致生物腐蚀和硫化物污染等环境危害。由于难以培养严格厌氧菌，寻找有效的DSR抑制剂一直具有挑战性。在本研究中，我们采用分子对接和100纳秒分子动力学（MD）模拟，筛选了248种微生物来源的化合物作为DSR抑制剂的潜力。基于对接分数，鉴定出9种命中化合物，其中脱氢柠檬苦苷A表现出最高的结合亲和力（-9.4千卡/摩尔），其次是西曲霉素θA和埃他霉素。氢键相互作用分析表明，包括Arg83、Arg101和Lys215在内的关键活性位点残基在配体结合中起重要作用。MD模拟揭示了DSR-化合物复合物之间不同的稳定性，其中阿苏加星A表现出最高的稳定性和最小的波动，而抗霉素A1和青霉素地美嗪A表现出最高的不稳定性。主成分分析（PCA）表明，与抗霉素A1、埃他霉素、西曲霉素θA和土曲霉毒素G形成的复合物具有更大的构象灵活性。结合自由能计算证实，脱氢柠檬苦苷A（-112.13千焦/摩尔）和嗜球果伞素（-107.66千焦/摩尔）与DSR的相互作用最为有利。此外，计算机环境毒性评估表明，一些化合物，如沙门菌素sx，具有较高的毒性风险，而其他化合物，如脱氢柠檬苦苷A，对环境的影响较小。总体而言，我们的研究结果突出了嗜球果伞素、阿苏加星A和脱氢柠檬苦苷A作为有前景的DSR抑制剂，值得进一步研究其在控制SRB中的潜在应用。
补充信息
在线版本包含可在10.1007/s40203-025-00367-9获取的补充材料。
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