用人工智能(AI)和分子动力学方法探索和设计天然产品中潜在的 SIRT2 抑制剂

IF 1.2 4区 医学 Q4 CHEMISTRY, MEDICINAL
Yangyang Ni, Juxia Bai, Yuqi Zhang, Haoran Qiao, Liqun Liang, Junfeng Wan, Yanyan Zhu, Haijing Cao, Huiyu Li, Qingjie Zhao
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引用次数: 0

摘要

背景包括sirtuins在内的组蛋白去乙酰化酶家族参与了广泛的细胞过程,并与神经退行性疾病密切相关。有关 sirtuins 的研究引起了广泛关注。然而,目前还没有有效的治疗药物。研究方法为了探索 SIRTs 的潜在抑制剂,我们首先使用 Auto- Dock Vina 方法筛选了中药中治疗神经疾病的 SIRT2 的四个潜在先导化合物。然后,通过分子动力学(MD)模拟方法,我们发现了这些中药抑制剂如何在原子水平上影响该蛋白。结果与讨论我们发现抑制剂与 SIRT2 之间的疏水相互作用至关重要。小分子对锌结合结构域的残基有很强的影响,显示出与信号通路的关系。最后,根据四种潜在中药抑制剂的构象特征和 MD 特性,我们利用 MolAICal 软件,采用 AI 方法,根据结合能、指纹相似性、三维相似性和 RO5 等参数设计了新的骨架分子。结论我们提出了 SIRT2 的候选抑制剂。我们的研究提供了一种新方法,可用于探索中药的潜在抑制剂。这有可能为创造有效的药物铺平道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Exploring and Designing Potential Inhibitors of SIRT2 in Natural Products by Artificial Intelligence (AI) and Molecular Dynamics Methods
Background:: The histone deacetylase family of proteins, which includes the sirtuins, participates in a wide range of cellular processes, and is intimately involved in neurodegenerative illnesses. The research on sirtuins has garnered a lot of interest. However, there are currently no effective therapeutic drugs. Methods:: In order to explore the potential inhibitors of SIRTs, we first screened four potential lead compounds of SIRT2 in Traditional Chinese Medicine (TCM) for nervous disease using the Auto- Dock Vina method. Then, with Molecular Dynamics (MD) simulation method, we discovered how these inhibitors from Traditional Chinese herbal medicines affect this protein at the atomic level. Results and Discussion:: We found hydrophobic interactions between inhibitors and SIRT2 to be crucial. The small molecules have been found to have strong effect on the residues in the zincbinding domain, exhibiting relationship with the signaling pathway. Finally, based on the conformational characteristics and the MD properties of the four potential inhibitors in TCM, we have designed the new skeleton molecules according to the parameters of binding energy, fingerprint similarity, 3D similarity, and RO5, with AI method using MolAICal software. Conclusion:: We have proposed the candidate inhibitor of SIRT2. Our research has provided a new approach that can be used to explore potential inhibitors from TCM. This could potentially pave the way for the creation of effective medicines.
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来源期刊
CiteScore
1.80
自引率
10.00%
发文量
245
审稿时长
3 months
期刊介绍: Aims & Scope Letters in Drug Design & Discovery publishes letters, mini-reviews, highlights and guest edited thematic issues in all areas of rational drug design and discovery including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, and structure-activity relationships. The emphasis is on publishing quality papers very rapidly by taking full advantage of latest Internet technology for both submission and review of manuscripts. The online journal is an essential reading to all pharmaceutical scientists involved in research in drug design and discovery.
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