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MSBack:使用受约束扩散的高粗粒度蛋白质的多尺度后映射

Curt Waltmann¹, Yihang Wang¹, Chengxi Yang

¹Department of Chemistry, Chicago Center for Theoretical Chemistry, Institute for Biophysical Dynamics, and James Franck Institute, The University of Chicago, Chicago, Illinois 60637, United States.

Journal of chemical theory and computation

|June 2, 2025

概括

我们开发了MSBack,这是一种新的扩散模型方法,可以从粗粒度模型中重建全原子蛋白质结构. 这促进了生物分子模拟和对病毒等复杂物体的结构分析.

科学领域:

生物物理学的生物物理.
计算生物学计算生物学
结构生物学结构生物学

背景情况:

粗粒度 (CG) 分子动力学模拟生物分子行为,但失去结构细节.
将CG模型逆向映射到全原子分辨率是具有挑战性的,特别是在低分辨率 (每残留物少于一个位点) 时.
低分辨率的CG模型对于模拟像病毒 (例如,SARS-CoV-2,HIV-1) 这样的大型复合体至关重要.

研究的目的:

开发一种方法,从高度粗粒的蛋白质结构中准确地重建所有原子.
为了应对在每个残留点下一个位置的分辨率下对蛋白质进行逆向映射的尚未解决的挑战.
为了能够对大型生物分子复合体进行详细的结构分析.

主要方法:

提出MSBack,这是一个扩散模型的方法,用于向后映射.
限制了扩散过程,使所有原子坐标与CG坐标相匹配.
在没有再培训的情况下利用现有的全原子结构的扰动.
基于物理的综合方法,用于细粒度的后映射.

主要成果:

MSBack 随机生成与CG坐标相匹配的α-碳痕迹.
成功地证明了成熟的HIV-1囊体的完整逆向映射.
实现了对背映射的HIV-1囊体结构的1 Å分辨率.
该方法适用于以大型复合体所需的分辨率模拟的蛋白质.

结论:

MSBack有效地从低分辨率的CG模型中重建全原子蛋白质结构.
这种方法克服了当前后映射技术的局限性.
能够对大型生物分子系统及其相互作用进行详细的结构洞察.

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