DNA结合蛋白的形状感知扩散性在DNA沿线经历旋转合的滑动动态
Shrawan Kumar Choudhary1, Kavana Priyadarshini Keshava1, Arnab Bhattacherjee1
1School of Computational and Integrative Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
The journal of physical chemistry. B
|November 29, 2025
概括
我们开发了BBXB,这是一个新的模型,可以预测DNA结合蛋白如何沿着DNA移动. 它准确地将蛋白质形状与滑动动力学联系起来,改进了旧模型.
科学领域:
- 生物物理学的生物物理.
- 计算生物学 计算生物学
- 分子动力学分子动力学
背景情况:
- DNA结合蛋白通过旋转合的滑动定位目标.
- 经典的Bagchi-Blainey-Xie (BBX) 模型使用了蛋白质的球形近似.
- 现有的模型缺乏详细的结构整合,无法准确地进行水力动力学预测.
研究的目的:
- 介绍BBXB,一种形状感知的DNA-蛋白滑动的水力动力学模型.
- 通过结合3D蛋白质结构和异构性来提高预测准确性.
- 建立一个无参数的框架,将分子形状与滑动动力学联系起来.
主要方法:
- 从使用Happel-Brenner积分的3D蛋白质结构中获得翻译和旋转摩擦.
- 纳入了蛋白质-DNA相互作用能量景观的粗度参数.
- 对各种DNA结合蛋白的实验扩散系数和水力动力学基准进行了验证BBXB.
主要成果:
- BBXB准确地复制了Lac抑制剂和hOgg1糖酶的实验扩散系数.
- 在27种蛋白质中,BBXB预测与SoMo/GRPY基准有很强的相关性 (R2 ≈ 0.99).
- 旋转阻力被确定为主要的消散因子,随着形状异型和DNA偏移而增加.
结论:
- BBXB为DNA-蛋白滑动提供了一个可预测的,无参数的水力动力学模型.
- 分子形状和异质性是1D滑动动态的关键决定因素.
- 该模型量化地将蛋白质结构与生物物理滑动机制联系起来.
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