通过分子动力学模拟探索针对副隐孢子虫乳酸脱氢酶的芳香紫苏植物化学物质的抗原虫机制

IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Archives of biochemistry and biophysics Pub Date : 2024-08-17 DOI:10.1016/j.abb.2024.110124
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引用次数: 0

摘要

众所周知,副隐孢子虫(C. parvum)是一种原生动物寄生虫,可诱发人类严重的胃肠道疾病。副孢子虫的一种蛋白质--乳酸脱氢酶(LDH)已被确定为开发有效抗感染药物的潜在治疗靶点。本研究利用计算药物发现方法来确定针对副猪嗜血杆菌 LDH 蛋白的潜在药物分子。在本研究中,我们对来自芳香茜草(Syzygium aromaticum,S. aromaticum)的 55 种植物化学物质进行了基于结构的虚拟筛选。在这一过程中,我们发现了四种植物化学物质,包括五倍子单宁 23、Eugeniin、Strictinin 和 Ellagitannin,它们与 LDH 蛋白具有显著的结合亲和力和动态稳定性。有趣的是,这四种化合物已被证实具有抗菌、抗病毒、抗炎和抗氧化特性。使用 Desmond 对对接复合物进行了 100 ns 的模拟,以检查其动态稳定性。最后,根据最后 10 ns 的 MD 轨迹计算自由结合能。在所有四种植物化学物质中,五倍子单宁 23 和艾拉单宁与目标蛋白质的结合亲和力和稳定性都相当高。这些研究结果表明,这些预测的芳香草植物化学物质可作为潜在的候选药物进行进一步的研究,以开发出有效的抗鼠李属真菌感染的药物。要确认它们作为 LDH 抑制剂的有效性和安全性,还需要进行体外和体内实验验证。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Exploring the anti-protozoal mechanisms of Syzygium aromaticum phytochemicals targeting Cryptosporidium parvum lactate dehydrogenase through molecular dynamics simulations

Cryptosporidium parvum (C. parvum), a protozoan parasite, is known to induce significant gastrointestinal disease in humans. Lactate dehydrogenase (LDH), a protein of C. parvum, has been identified as a potential therapeutic target for developing effective drugs against infection. This study utilized a computational drug discovery approach to identify potential drug molecules against the LDH protein of C. parvum. In the present investigation, we conducted a structure-based virtual screening of 55 phytochemicals from the Syzygium aromaticum (S. aromaticum). This process identified four phytochemicals, including Gallotannin 23, Eugeniin, Strictinin, and Ellagitannin, that demonstrated significant binding affinity and dynamic stability with LDH protein. Interestingly, these four compounds have been documented to possess antibacterial, antiviral, anti-inflammatory, and antioxidant properties. The docked complexes were simulated for 100 ns using Desmond to check the dynamic stability. Finally, the free binding energy was computed from the last 10ns MD trajectories. Gallotannin 23 and Ellagitannin exhibited considerable binding affinity and stability with the target protein among all four phytochemicals. These findings suggest that these predicted phytochemicals from S. aromaticum could be further explored as potential hit candidates for developing effective drugs against C. parvum infection. The in vitro and in vivo experimental validation is still required to confirm their efficacy and safety as LDH inhibitors.

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来源期刊
Archives of biochemistry and biophysics
Archives of biochemistry and biophysics 生物-生化与分子生物学
CiteScore
7.40
自引率
0.00%
发文量
245
审稿时长
26 days
期刊介绍: Archives of Biochemistry and Biophysics publishes quality original articles and reviews in the developing areas of biochemistry and biophysics. Research Areas Include: • Enzyme and protein structure, function, regulation. Folding, turnover, and post-translational processing • Biological oxidations, free radical reactions, redox signaling, oxygenases, P450 reactions • Signal transduction, receptors, membrane transport, intracellular signals. Cellular and integrated metabolism.
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