两性聚电解质相行为的简单显式溶剂模型及其对生物分子凝聚体介电效应的影响
A Simple Explicit-Solvent Model of Polyampholyte Phase Behaviors and its Ramifications for Dielectric Effects in Biomolecular Condensates
摘要：
生物分子凝聚体，如无膜细胞器，由液液相分离（LLPS）支撑，是重要的生理功能，静电-在其他相互作用类型-是一个突出的力量，在他们的组装。内在无序蛋白（IDP）和其他生物分子的电荷相互作用对水介质环境敏感。由于蛋白质的相对介电常数显著低于水的相对介电常数，因此IDP冷凝物的内部是相对低介电状态，除了其对客户分子的可能的功能性影响之外，其应促进支架IDP之间的更强的静电相互作用。为了深入了解这种LLPS诱导的介电异质性，特别是解决低介电凝聚相是否需要更有利的LLPS比假设IDP静电相互作用均匀调制的纯溶剂的介电常数较高，我们考虑了一个简化的多链模型的聚两性电解质浸泡在明确的溶剂，要么极化或拥有永久偶极子。值得注意的是，这些系统的模拟相行为表现出轻微到中度的差异，从那些使用隐式溶剂模型与均匀的相对介电常数等于纯溶剂。通过使用无规相近似和聚合物场论模拟在这里开发的理论处理的支持下，这些观察结果表明在凝聚相中的聚两性电解质之间的有利的溶剂介导的相互作用和在稀相中的有利的聚两性电解质-溶剂相互作用之间的效应的部分补偿，通常仅从由LLPS本身引起的非常介电的不均匀性中获得总体LLPS倾向的微小增强。这一原则的进一步后果进行了讨论。
英文摘要：
Biomolecular condensates such as membraneless organelles, underpinned by liquid-liquid phase separation (LLPS), are important for physiological function, with electrostatics -- among other interaction types -- being a prominent force in their assembly. Charge interactions of intrinsically disordered proteins (IDPs) and other biomolecules are sensitive to the aqueous dielectric environment. Because the relative permittivity of protein is significantly lower than that of water, the interior of an IDP condensate is a relatively low-dielectric regime, which, aside from its possible functional effects on client molecules, should facilitate stronger electrostatic interactions among the scaffold IDPs. To gain insight into this LLPS-induced dielectric heterogeneity, addressing in particular whether a low-dielectric condensed phase entails more favorable LLPS than that posited by assuming IDP electrostatic interactions are uniformly modulated by the higher dielectric constant of the pure solvent, we consider a simplified multiple-chain model of polyampholytes immersed in explicit solvents that are either polarizable or possess a permanent dipole. Notably, simulated phase behaviors of these systems exhibit only minor to moderate differences from those obtained using implicit-solvent models with a uniform relative permittivity equals to that of pure solvent. Buttressed by theoretical treatments developed here using random phase approximation and polymer field-theoretic simulations, these observations indicate a partial compensation of effects between favorable solvent-mediated interactions among the polyampholytes in the condensed phase and favorable polyampholyte-solvent interactions in the dilute phase, often netting only a minor enhancement of overall LLPS propensity from the very dielectric heterogeneity that arises from the LLPS itself. Further ramifications of this principle are discussed.
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