标题： 无序蛋白质凝聚物的粗粒度残基模型：简单电荷模式参数的适用性与局限性 显示英文标题

标题： Coarse-Grained Residue-Based Models of Disordered Protein Condensates: Utility and Limitations of Simple Charge Pattern Parameters

摘要： 由蛋白质和核酸相分离支撑的生物分子凝聚物在生物过程中起着关键作用。 为了获得其遗传基础的物理洞察，我们研究了固有无序蛋白（IDPs）的液-液相分离（LLPS）如何依赖于其序列电荷模式，使用了一个连续朗之万链模型，其中每个氨基酸残基由一个珠子表示。 电荷模式通过“块状度”度量$\kappa$和“序列电荷装饰”（SCD）参数来表征。 与随机相位近似（RPA）理论和格点模拟一致，对于一组序列来说，LLPS倾向性（由临界温度$T^*_{\rm cr}$表征）随着 SCD 变得越来越负而增加，这些序列的$\kappa$和$-$SCD 之间存在正相关性。 相对于 RPA，模拟的$T^*_{\rm cr}$的序列依赖性变化通常——尽管并非总是——较小，而模拟的临界体积分数则更高。 然而，对于一组表现出$\kappa$与$-$SCD 之间反相关的序列，模拟得到的$T^*_{\rm cr}$对这些参数不敏感。 此外，我们发现允许强静电排斥的块状序列可以导致符合 RPA 规定的向上凹的共存曲线，但严格交替电荷序列的 LLPS 倾向可能被 RPA 和格子模型高估了，因为该序列的链间稳定化需要在真实空间中难以实现的空间排列。 这些结果有助于明确电荷模式参数和 RPA 的适用性和局限性，指出了为合理解释新观察到的细微差别所需进一步努力的方向。 显示英文摘要

摘要： Biomolecular condensates undergirded by phase separations of proteins and nucleic acids serve crucial biological functions. To gain physical insights into their genetic basis, we study how liquid-liquid phase separation (LLPS) of intrinsically disordered proteins (IDPs) depends on their sequence charge patterns using a continuum Langevin chain model wherein each amino acid residue is represented by a single bead. Charge patterns are characterized by the `blockiness' measure $\kappa$ and the `sequence charge decoration' (SCD) parameter. Consistent with random phase approximation (RPA) theory and lattice simulations, LLPS propensity as characterized by critical temperature $T^*_{\rm cr}$ increases with increasingly negative SCD for a set of sequences showing a positive correlation between $\kappa$ and $-$SCD. Relative to RPA, the simulated sequence-dependent variation in $T^*_{\rm cr}$ is often---though not always---smaller, whereas the simulated critical volume fractions are higher. However, for a set of sequences exhibiting an anti-correlation between $\kappa$ and $-$SCD, the simulated $T^*_{\rm cr}$'s are quite insensitive to either parameters. Additionally, we find that blocky sequences that allow for strong electrostatic repulsion can lead to coexistence curves with upward concavity as stipulated by RPA, but the LLPS propensity of a strictly alternating charge sequence was likely overestimated by RPA and lattice models because interchain stabilization of this sequence requires spatial alignments that are difficult to achieve in real space. These results help delineate the utility and limitations of the charge pattern parameters and of RPA, pointing to further efforts necessary for rationalizing the newly observed subtleties.