绑定激进分子与粘附G蛋白合受体结合的机制
Keya Joshi1,2, Yinglong Miao1,2
1Bioinformatics and Computational Biology Program, University of North Carolina-Chapel Hill (UNC-CH), Chapel Hill, North Carolina 27599, United States.
The journal of physical chemistry. B
|December 22, 2025
概括
粘附G蛋白结合受体 (ADGRs) 的激活涉及一个绑定的激动剂 (TA) 从β链转变为α螺旋. 我们的模拟揭示了这种动态结合机制,有助于设计ADGR调节器.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 计算生物学 计算生物学
背景情况:
- 粘附G蛋白结合受体 (ADGRs) 使用绑定激动剂 (TA) 进行激活.
- 在ADGR激活时,TA经历了从β链到α螺旋的构造变化.
- 关于TA结合和形状变化的确切机制尚不清楚.
研究的目的:
- 阐明TA与ADGRD结合的动态机制1.
- 为了研究在ADGR激活过程中TA的构造过渡.
- 为了确定TA结合途径中的关键中间体.
主要方法:
- 全原子增强采样模拟. 全原子增强采样模拟.
- 酸高斯加速分子动力学 (Pep-GaMD) 方法.
- 在Gs蛋白存在或不存在的情况下对ADGRD1的模拟.
主要成果:
- 佩普-GaMD模拟捕获了自发的TA与ADGRD1.1的结合.
- 观察到从延伸的β链到U形α螺旋的TA形状转变.
- 识别了低能量构造和明显的活跃/不活跃ADGRD1状态.
结论:
- 这项研究揭示了TA与ADGRs结合的动态机制.
- 结果提供了对ADGR激活途径的见解.
- 这项工作有助于合理设计基于的ADGR调节器.
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