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主导性分析:一种揭示多组分系统中生物分子凝聚物形成的主要能量贡献的形式体系。

Dominance Analysis: A formalism to uncover dominant energetic contributions to biomolecular condensate formation in multicomponent systems.

作者信息

Qian Daoyuan, Ausserwoger Hannes, Sneideris Tomas, Farag Mina, Pappu Rohit V, Knowles Tuomas P J

出版信息

bioRxiv. 2024 Mar 22:2023.06.12.544666. doi: 10.1101/2023.06.12.544666.

Abstract

Phase separation in aqueous solutions of macromolecules is thought to underlie the generation of biomolecular condensates in cells. Condensates are membraneless bodies, representing dense, macromolecule-rich phases that coexist with the dilute, macromolecule-deficient phase. In cells, condensates comprise hundreds of different macromolecular and small molecule solutes. Do all components contribute equally or very differently to the driving forces for phase separation? Currently, we lack a coherent formalism to answer this question, a gap we remedy in this work through the introduction of a formalism we term energy dominance analysis. This approach rests on model-free analysis of shapes of the dilute arms of phase boundaries, slopes of tie lines, and changes to dilute phase concentrations in response to perturbations of concentrations of different solutes. We present the formalism that underlies dominance analysis, and establish its accuracy and flexibility by deploying it to analyse phase spaces probed , and .

摘要

大分子水溶液中的相分离被认为是细胞中生物分子凝聚物形成的基础。凝聚物是无膜的物体,代表与稀释的、大分子缺乏的相共存的致密、富含大分子的相。在细胞中,凝聚物包含数百种不同的大分子和小分子溶质。所有组分对相分离驱动力的贡献是相同还是差异很大呢?目前,我们缺乏一个连贯的形式体系来回答这个问题,在这项工作中,我们通过引入一种我们称之为能量优势分析的形式体系来弥补这一差距。这种方法基于对相边界稀释臂形状、系线斜率以及不同溶质浓度扰动引起的稀释相浓度变化的无模型分析。我们提出了优势分析的形式体系,并通过将其应用于分析所探测的相空间来确定其准确性和灵活性。

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