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基于结构的化学信息学和分子动力学对潜在的SIRT6抑制剂进行分析

Ali Al-Samydai¹, Farah Al-Mamoori², Amal Mayyas³

¹Pharmacological and Diagnostic Research Centre, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman, Jordan.

Molecular diversity

|July 12, 2025

概括

研究人员使用计算方法确定了针对Sirtuin-6 (SIRT6),这是衰老和代谢疾病中的关键蛋白质的潜在新药候选者. 这项研究为发现用于治疗开发的新型SIRT6抑制剂提供了框架.

科学领域:

生物化学和分子生物学
计算化学计算化学
药理学药理学是指药理学的学科.

背景情况:

赛尔图因-6 (SIRT6) 是一种关键的NAD+依赖性脱乙酶,参与维持基因组稳定,代谢调节和细胞应激反应.
SIRT6是代谢和与年龄有关的疾病的有希望的治疗点,但强大的调节器很少.
识别有效的SIRT6抑制剂对于开发新疗法至关重要.

研究的目的:

使用集成计算方法探索针对Sirtuin-6 (SIRT6) 的新型抑制候选药物.
开发和验证SIRT6抑制剂的强大的定量结构-活性关系 (QSAR) 模型.
阐明SIRT6的功能网络,并确定具有稳定的结合相互作用的化合物.

主要方法:

利用化学信息学,网络药理学,分子对接和分子动力学 (MD) 模拟.
使用随机森林算法开发了多指纹QSAR模型,经过严格验证.
进行网络分析以确定SIRT6相关途径和对接/MD模拟用于候选评估.

主要成果:

QSAR模型对SIRT6调节器具有很高的预测能力.
网络药理学揭示了SIRT6在NAD+生物合成和通过NAMPT和HIF1A等蛋白质的细胞应激中的作用.
分子对接和MD模拟确定了Quercetin (CHEMBL50) 和CHEMBL4217987作为具有稳定结合SIRT6.7的有希望的候选者.

结论:

这项研究提出了一个验证的计算框架,用于发现SIRT6抑制剂.
鉴定到的支架 (Quercetin和CHEMBL4217987) 需要进一步的实验研究.
这项研究促进了针对SIRT6治疗代谢和衰老相关疾病的治疗策略的开发.

关键词:

MM-GBSA 的绑定能量是 MM-GBSA 的绑定能量.分子对接是分子对接.分子动力学模拟模型网络药理学网络药理学在QSAR建模中使用QSAR模型.锡尔图因-6 (SIRT6) 是一种

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