Phase separation is thought to underlie spatial and temporal organization that is required for controlling biochemical reactions in cells. Multivalence of interaction motifs, also known as stickers, is a defining feature of proteins that drive phase separation. Intrinsically disordered proteins with stickers uniformly distributed along the linear sequence can serve as scaffold molecules that drive phase separation. The sequence-intrinsic contributions of disordered proteins to phase separation can be discerned by computing or measuring sequence-specific phase diagrams. These help to delineate the combinations of protein concentration and a suitable control parameter, such as temperature, that support phase separation. Here, we present an approach that combines detailed simulations with a numerical adaptation of an analytical Gaussian cluster theory to enable the calculation of sequence-specific phase diagrams. Our approach leverages the known equivalence between the driving forces for single-chain collapse in dilute solutions and the driving forces for phase separation in concentrated solutions. We demonstrate the application of the theory-aided computations through calculation of phase diagrams for a set of archetypal intrinsically disordered low-complexity domains. We also leverage theories to compute sequence-specific percolation lines and thereby provide a thermodynamic framework for hardening transitions that have been observed for many biomolecular condensates.

中文翻译：

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将线圈到球体的转变连接到本质无序蛋白质的完整相图


相分离被认为是控制细胞生化反应所需的空间和时间组织的基础。多价相互作用基序，也称为贴纸，是驱动相分离的蛋白质的一个定义特征。具有沿着线性序列均匀分布的贴纸的本质无序的蛋白质可以充当驱动相分离的支架分子。无序蛋白质对相分离的序列固有贡献可以通过计算或测量序列特异性相图来辨别。这些有助于描述蛋白质浓度和支持相分离的合适控制参数（例如温度）的组合。在这里，我们提出了一种将详细模拟与分析高斯簇理论的数值适应相结合的方法，以能够计算特定序列的相图。我们的方法利用了稀溶液中单链塌陷的驱动力与浓溶液中相分离的驱动力之间已知的等价性。我们通过计算一组原型本质上无序的低复杂性域的相图来演示理论辅助计算的应用。我们还利用理论来计算序列特异性渗滤线，从而为在许多生物分子凝聚物中观察到的硬化转变提供热力学框架。