中国物理B ›› 2025, Vol. 34 ›› Issue (5): 58301-058301.doi: 10.1088/1674-1056/adbd16

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Protein aging dynamics: A perspective from non-equilibrium coarse-grained models

Yue Shan(单月)1, Chun-Lai Ren(任春来)1,2,†, and Yu-Qiang Ma(马余强)1,2   

  1. 1 National Laboratory of Solid State Microstructures and Department of Physics, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, China;
    2 Hefei National Laboratory, Hefei 230088, China
  • 收稿日期:2025-01-04 修回日期:2025-02-09 接受日期:2025-03-06 出版日期:2025-04-18 发布日期:2025-04-18
  • 通讯作者: Chun-Lai Ren E-mail:chunlair@nju.edu.cn
  • 基金资助:
    We are grateful to the High-Performance Computing Center (HPCC) of Nanjing University for the numerical calculations in this paper on its blade cluster system. This work is supported by the National Key Research and Development Program of China (Grant No. 2022YFA1405000), the National Natural Science Foundation of China (Grant Nos. 12274212, 12347102, and 12174184), and Innovation Program for Quantum Science and Technology (Grant No. 2024ZD0300101).

Protein aging dynamics: A perspective from non-equilibrium coarse-grained models

Yue Shan(单月)1, Chun-Lai Ren(任春来)1,2,†, and Yu-Qiang Ma(马余强)1,2   

  1. 1 National Laboratory of Solid State Microstructures and Department of Physics, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, China;
    2 Hefei National Laboratory, Hefei 230088, China
  • Received:2025-01-04 Revised:2025-02-09 Accepted:2025-03-06 Online:2025-04-18 Published:2025-04-18
  • Contact: Chun-Lai Ren E-mail:chunlair@nju.edu.cn
  • Supported by:
    We are grateful to the High-Performance Computing Center (HPCC) of Nanjing University for the numerical calculations in this paper on its blade cluster system. This work is supported by the National Key Research and Development Program of China (Grant No. 2022YFA1405000), the National Natural Science Foundation of China (Grant Nos. 12274212, 12347102, and 12174184), and Innovation Program for Quantum Science and Technology (Grant No. 2024ZD0300101).

摘要: The aging of biomolecular condensates has been implicated in the pathogenesis of various neurodegenerative diseases, characterized by a transition from a physiologically liquid-like state to a pathologically ordered structure. However, the mechanisms governing the formation of these pathological aggregates remain poorly understood. To address this, the present study utilizes coarse-grained molecular dynamics simulations based on Langevin dynamics to explore the structural, dynamical, and material property changes of protein condensates during the aging process. Here, we further develop a non-equilibrium simulation algorithm that not only captures the characteristics of time-dependent amount of aging beads but also reflects the structural information of chain-like connections between aging beads. Our findings reveal that aging induces compaction of the condensates, accompanied by a decrease in diffusion rates and an increase in viscosity. Further analysis suggests that the heterogeneous diffusivity within the condensates may drive the aging process to initiate preferentially at the condensate surface. Our simulation results align with the experimental phenomena and provide a clear physical picture of the aging dynamics.

关键词: protein condensates, aging, coarse-grained simulation, liquid-to-solid transition

Abstract: The aging of biomolecular condensates has been implicated in the pathogenesis of various neurodegenerative diseases, characterized by a transition from a physiologically liquid-like state to a pathologically ordered structure. However, the mechanisms governing the formation of these pathological aggregates remain poorly understood. To address this, the present study utilizes coarse-grained molecular dynamics simulations based on Langevin dynamics to explore the structural, dynamical, and material property changes of protein condensates during the aging process. Here, we further develop a non-equilibrium simulation algorithm that not only captures the characteristics of time-dependent amount of aging beads but also reflects the structural information of chain-like connections between aging beads. Our findings reveal that aging induces compaction of the condensates, accompanied by a decrease in diffusion rates and an increase in viscosity. Further analysis suggests that the heterogeneous diffusivity within the condensates may drive the aging process to initiate preferentially at the condensate surface. Our simulation results align with the experimental phenomena and provide a clear physical picture of the aging dynamics.

Key words: protein condensates, aging, coarse-grained simulation, liquid-to-solid transition

中图分类号:  (Molecular dynamics, Brownian dynamics)

  • 83.10.Mj
87.15.H- (Dynamics of biomolecules) 87.15.km (Protein-protein interactions) 87.15.nr (Aggregation)