研究pH对胰岛素纤维素稳定性的影响:分子动力学见解
Yasaman Mahmoodi1, Shirin Jalali1, Shirin Shahabadi1
1Department of Nanobiotechnology and Biomimetics, School of Life Sciences Engineering, College of Interdisciplinary Science and Technology, University of Tehran, Tehran, 14395-1561, Iran.
Journal of molecular graphics & modelling
|December 13, 2025
概括
胰岛素粉样纤维的稳定性取决于pH值. 中性pH通过静电排斥破坏纤维的稳定性,而酸性pH通过更紧的包装增强稳定性,影响胰岛素衍生性粉化症.
科学领域:
- 生物化学 生化学
- 结构生物学 结构生物学
- 计算生物物理学的计算生物物理学
背景情况:
- 胰岛素粉样纤维素与胰岛素衍生的粉样症等临床问题有关.
- 了解纤维素稳定性对于治疗干预至关重要.
研究的目的:
- 为了研究pH值对胰岛素粉样纤维的结构稳定性的影响.
- 阐明pH取决于纤维细胞不稳定性的分子机制.
主要方法:
- 分子动力学 (MD) 模拟用于在中性 (pH7) 和酸性 (pH2) 条件下建模胰岛素纤维.
- 用水化表征和主要成分分析 (PCA) 来分析结构动态.
主要成果:
- 在中性的pH值下,去的谷氨酸残留物会引起排斥,减少键并破坏纤维的稳定.
- 酸性pH导致质子化,减少排斥,增加纤维的紧性和稳定性.
- 在pH 7的纤维显示出更大的水分和集体运动,表明与pH 2相比稳定性降低.
结论:
- pH通过调节静电相互作用和结合,显著影响胰岛素纤维结构和稳定性.
- 这些发现为开发抗胰岛素衍生性粉症的策略和改善胰岛素治疗结果提供了机制性见解.
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