识别与昼夜时钟机械相互作用的饮食化合物:分子对接和结构相似性分析
Eleni Pitsillou1, Julia J Liang1, Raymond C Beh1
1Epigenomic Medicine Laboratory at ProspED, Carlton, VIC, 3053, Australia; School of Science, STEM College, RMIT University, VIC, 3001, Australia.
Journal of molecular graphics & modelling
|June 1, 2023
概括
研究人员探索了饮食化合物来调节分子钟,这是身体节律的关键调节者. 他们确定了与RORα/γ受体相互作用的潜在治疗剂,为治疗与时钟相关的疾病提供了新的途径.
科学领域:
- 生物化学 生物化学
- 药理学 药理学是指药理学的学科.
- 时间生物学 时间生物学
背景情况:
- 分子时钟控制着昼夜节律,这是生理过程中必不可少的.
- 分子时钟的失调与各种疾病有关.
- 小分子调制器为与时钟相关的疾病提供了一个有希望的治疗策略.
研究的目的:
- 为了建模人类的昼夜运动运动输出循环卡普特 (CLOCK) 蛋白质,并确定连接体结合位点.
- 研究CLK8的结合模式,并探索用于时钟调节的食化合物.
- 为了确定与视网膜酸相关的孤儿受体 (RORα/γ) 相互作用的饮食化合物,以获得治疗潜力.
主要方法:
- 人类CLOCK蛋白的同质模型.
- 分子对接以分析联体蛋白相互作用.
- 对RORα/γ相互作用的选择饮食化合物的分子相似性和对接分析.
主要成果:
- 在CLOCK蛋白上确定了潜在的连接体结合点.
- 描述了对照化合物CLK8.8的结合模式.
- 发现了烯酸甲基,3-epi-lupeol和taraxasterol作为潜在的RORα/γ相互作用化合物.
结论:
- 饮食化合物可以成为分子钟小分子调节器的来源.
- 烯酸甲基,3-epi-lupeol和taraxasterol可能调节RORα/γ活性,影响分子时钟.
- 需要进一步的研究来验证这些化合物作为治疗时钟相关疾病的治疗剂.
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