A Lattice Model of Charge-Pattern-Dependent Polyampholyte Phase Separation
A Lattice Model of Charge-Pattern-Dependent Polyampholyte Phase Separation
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DOI：
10.1021/acs.jpcb.7b11723
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发表时间：
2018-05-31
影响因子：
3.3
通讯作者：
Chan, Hue Sun
中科院分区：
文献类型：
--
作者：
Das, Suman;Eisen, Adam;Chan, Hue Sun
鉴于近年来在本质无序蛋白质(IDPs)的液-液相分离(LLP)生物物理方面的强烈实验和理论兴趣，构建了链分子在简单立方晶格上自回避行走的杂多分子模型，以研究相行为如何依赖于链上单体的序列。为了解决相关的一般原理，我们主要关注两个完全带电的50单体序列，它们的电荷模式明显不同。在我们的模型中，每个单体占据一个晶格位置，并且所有单体通过屏蔽的成对库仑势相互作用。相图是通过在多个温度下对尺寸从52x52x52到246x246x246的盒子中的300个链进行广泛的蒙特卡罗采样来模拟大量不同的体系来获得的，每个体系中的总聚合物体积分数为0.001到0.1%。模型体系中的相分离特征是通过单体间最近邻晶格接触连接的大团簇的出现和局部聚合物密度的大幅波动。这两个序列的模拟相分离的临界温度T-cr显著不同，因此具有更“块状”电荷模式的序列表现出显著更高的相分离倾向。这一趋势与我们的序列特异性随机相近似(RPA)聚合物理论是一致的，但模拟的T-cr随先前提出的“序列电荷装饰”图案参数的变化比RPA预测的要温和。讨论了我们的发现对发展IDP LLP的分析理论和模拟协议的影响。
In view of recent intense experimental and theoretical interests in the biophysics of liquid-liquid phase separation (LLPS) of intrinsically disordered proteins (IDPs), heteropolymer models with chain molecules configured as self-avoiding walks on the simple cubic lattice are constructed to study how phase behaviors depend on the sequence of monomers along the chains. To address pertinent general principles, we focus primarily on two fully charged 50-monomer sequences with significantly different charge patterns. Each monomer in our models occupies a single lattice site, and all monomers interact via a screened pairwise Coulomb potential. Phase diagrams are obtained by extensive Monte Carlo sampling performed at multiple temperatures on ensembles of 300 chains in boxes of sizes ranging from 52 x 52 X 52 to 246 x 246 X 246 to simulate a large number of different systems with the overall polymer volume fraction 0 in each system varying from 0.001 to 0.1. Phase separation in the model systems is characterized by the emergence of a large cluster connected by intermonomer nearest-neighbor lattice contacts and by large fluctuations in local polymer density. The simulated critical temperatures, T-cr, of phase separation for the two sequences differ significantly, whereby the sequence with a more "blocky" charge pattern exhibits a substantially higher propensity to phase separate. The trend is consistent with our sequence-specific random-phase-approximation (RPA) polymer theory, but the variation of the simulated T-cr with a previously proposed "sequence charge decoration" pattern parameter is milder than that predicted by RPA. Ramifications of our findings for the development of analytical theory and simulation protocols of IDP LLPS are discussed.