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计算机模拟表明液-液相分离增强了自组装。

Computer Simulations Show That Liquid-Liquid Phase Separation Enhances Self-Assembly.

作者信息

Frechette Layne B, Sundararajan Naren, Caballero Fernando, Trubiano Anthony, Hagan Michael F

机构信息

Martin Fisher School of Physics, Brandeis University, Waltham, Massachusetts 02453, United States.

出版信息

ACS Nano. 2025 Aug 26;19(33):30275-30291. doi: 10.1021/acsnano.5c08120. Epub 2025 Aug 9.


DOI:10.1021/acsnano.5c08120
PMID:40782375
Abstract

Biomolecular condensates are liquid- or gel-like droplets of proteins and nucleic acids formed at least in part through liquid-liquid phase separation. Condensates enable diverse functions of cells and the pathogens that infect them, including self-assembly reactions. For example, it has been shown that many viruses form condensates within their host cells to compartmentalize capsid assembly and packaging of the viral genome. Yet, the physical principles controlling condensate-mediated self-assembly remain incompletely understood. In this article, we use coarse-grained molecular dynamics simulations to study the effect of a condensate on the assembly of icosahedral capsids. The capsid subunits are represented by simple shape-based models to enable simulating a wide range of length and time scales, while the condensate is modeled implicitly to study the effects of phase separation independent of the molecular details of biomolecular condensates. Our results show that condensates can significantly enhance assembly rates, yields, and robustness to parameter variations, consistent with previous theoretical predictions. However, extending beyond those predictions, the computational models also show that excluded volume enables control over the number of capsids that assemble within condensates. Moreover, long-lived aberrant off-pathway assembly intermediates can suppress yields within condensates. In addition to elucidating condensate-mediated assembly of viruses and other biological structures, these results may guide the use of condensates as a generic route to enhance and control self-assembly in human-engineered systems.

摘要

生物分子凝聚物是蛋白质和核酸形成的液滴或凝胶状液滴,至少部分是通过液-液相分离形成的。凝聚物实现了细胞及其感染病原体的多种功能,包括自组装反应。例如,已经表明许多病毒在其宿主细胞内形成凝聚物,以分隔衣壳组装和病毒基因组的包装。然而,控制凝聚物介导的自组装的物理原理仍未完全理解。在本文中,我们使用粗粒度分子动力学模拟来研究凝聚物对二十面体衣壳组装的影响。衣壳亚基由基于简单形状的模型表示,以能够模拟广泛的长度和时间尺度,而凝聚物则进行隐式建模,以研究相分离的影响,而与生物分子凝聚物的分子细节无关。我们的结果表明,凝聚物可以显著提高组装速率、产量以及对参数变化的稳健性,这与先前的理论预测一致。然而,超出这些预测的是,计算模型还表明,排除体积能够控制在凝聚物内组装的衣壳数量。此外,长寿命的异常非途径组装中间体可以抑制凝聚物内的产量。除了阐明凝聚物介导的病毒和其他生物结构的组装外,这些结果可能指导将凝聚物用作增强和控制人工系统中自组装的通用途径。

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Computer Simulations Show That Liquid-Liquid Phase Separation Enhances Self-Assembly.

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本文引用的文献

[1]
Nucleocapsid assembly drives Ebola viral factory maturation and dispersion.

Cell. 2025-2-6

[2]
Identifying Sequence Effects on Chain Dimensions of Disordered Proteins by Integrating Experiments and Simulations.

JACS Au. 2024-11-14

[3]
Hierarchical design of pseudosymmetric protein nanocages.

Nature. 2025-2

[4]
The exchange dynamics of biomolecular condensates.

Elife. 2024-9-25

[5]
Emergence of Multiphase Condensates from a Limited Set of Chemical Building Blocks.

J Chem Theory Comput. 2024-8-13

[6]
Physical limits to acceleration of enzymatic reactions inside phase-separated compartments.

Phys Rev E. 2024-6

[7]
Economical routes to size-specific assembly of self-closing structures.

Sci Adv. 2024-7-5

[8]
Fundamental Aspects of Phase-Separated Biomolecular Condensates.

Chem Rev. 2024-7-10

[9]
Heterogeneous nucleation and growth of sessile chemically active droplets.

J Chem Phys. 2024-6-14

[10]
Expanding the molecular language of protein liquid-liquid phase separation.

Nat Chem. 2024-7

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