Theory and Simulation of Multiphase Coexistence in Biomolecular Mixtures
Theory and Simulation of Multiphase Coexistence in Biomolecular Mixtures
复制标题
生物分子混合物中多相共存的理论与模拟
DOI：
10.1021/acs.jctc.3c00198
复制
发表时间：
2023
影响因子：
5.5
通讯作者：
Jacobs, William M.
中科院分区：
文献类型：
--
作者：
Jacobs, William M.
生物分子凝聚体构成了活细胞中一种新认识的空间组织形式。尽管许多凝析物被认为是相分离的结果，但决定异质生物分子混合物相行为的物理化学性质才刚刚开始被探索。理论和模拟为探索分子决定因素（如蛋白质和RNA序列）之间的关系以及在如此复杂的环境中相分离凝聚物的出现提供了宝贵的工具。本文综述了相分离为许多共存相的生物分子混合物的预测和计算设计方面的最新进展。首先，我们回顾了使用理论模型和统计方法来理解数百或数千种混合物的相行为的努力。然后，我们描述了发展分析理论和粗粒度模拟模型的进展，以预测多相凝析油的分子细节，以便与生物物理实验接触。最后，我们总结了在活细胞中模拟生物分子混合物的非均匀空间组织所面临的挑战。
Biomolecular condensates constitute a newly recognized form of spatial organization in living cells. Although many condensates are believed to form as a result of phase separation, the physicochemical properties that determine the phase behavior of heterogeneous biomolecular mixtures are only beginning to be explored. Theory and simulation provide invaluable tools for probing the relationship between molecular determinants, such as protein and RNA sequences, and the emergence of phase-separated condensates in such complex environments. This review covers recent advances in the prediction and computational design of biomolecular mixtures that phase-separate into many coexisting phases. First, we review efforts to understand the phase behavior of mixtures with hundreds or thousands of species using theoretical models and statistical approaches. We then describe progress in developing analytical theories and coarse-grained simulation models to predict multiphase condensates with the molecular detail required to make contact with biophysical experiments. We conclude by summarizing the challenges ahead for modeling the inhomogeneous spatial organization of biomolecular mixtures in living cells.