Liquid-liquid phase separation (LLPS) is widely utilized by the cell to organize and regulate various biochemical processes. Although the LLPS of proteins is known to occur in a sequence dependent manner, it is unclear how sequence properties dictate the nature of the phase transition and thereby influence condensed phase morphology. In this work, we have utilized grand canonical Monte Carlo simulations for a simple coarse-grained model of disordered proteins to systematically investigate how sequence distribution, sticker fraction and chain length influence the phase behavior and regulate the formation of finite-size aggregates preempting macroscopic phase separation for some sequences. We demonstrate that a normalized sequence charge decoration (SCD) parameter establishes a ``soft" criterion for predicting the underlying phase transition of a model protein. Additionally, we find that this order parameter is strongly correlated to the critical density for phase separation, highlighting an unambiguous connection between sequence distribution and condensed phase density. Results obtained from an analysis of the order parameter reveals that at sufficiently long chain lengths, the vast majority of sequences are likely to phase separate. Our results predict that classical LLPS should be the dominant phase transition for disordered proteins and suggests a possible reason behind recent findings of widespread phase separation throughout living cells.

中文翻译：

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模型无序蛋白质的相分离与聚集行为

液-液相分离 (LLPS) 被细胞广泛用于组织和调节各种生化过程。尽管已知蛋白质的 LLPS 以依赖于序列的方式发生，但尚不清楚序列特性如何决定相变的性质，从而影响凝聚相形态。在这项工作中，我们利用对无序蛋白质的简单粗粒度模型的大规范蒙特卡罗模拟来系统地研究序列分布、粘着分数和链长如何影响相行为并调节抢占宏观相的有限尺寸聚集体的形成某些序列的分离。我们证明了归一化序列电荷修饰 (SCD) 参数建立了一个“软” 预测模型蛋白质潜在相变的标准。此外，我们发现该顺序参数与相分离的临界密度密切相关，突出了序列分布和凝聚相密度之间的明确联系。从顺序参数分析获得的结果表明，在足够长的链长度下，绝大多数序列可能会发生相分离。我们的结果预测，经典的 LLPS 应该是无序蛋白质的主要相变，并提出了最近在整个活细胞中广泛相分离的发现背后的可能原因。突出了序列分布和凝聚相密度之间的明确联系。从顺序参数分析获得的结果表明，在足够长的链长度下，绝大多数序列可能会发生相分离。我们的结果预测，经典的 LLPS 应该是无序蛋白质的主要相变，并提出了最近在整个活细胞中广泛相分离的发现背后的可能原因。突出了序列分布和凝聚相密度之间的明确联系。从顺序参数分析获得的结果表明，在足够长的链长度下，绝大多数序列可能会发生相分离。我们的结果预测，经典的 LLPS 应该是无序蛋白质的主要相变，并提出了最近在整个活细胞中广泛相分离的发现背后的可能原因。