Liquid–Liquid Phase Separation As the Second Step of Complex Coacervation
Liquid–Liquid Phase Separation As the Second Step of Complex Coacervation
复制标题
液体-液相分离作为复合凝聚的第二步
DOI：
10.1021/acs.jpcb.0c07349
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Yethiraj, Arun
中科院分区：
文献类型：
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作者：
Singh, Aditya N.;Yethiraj, Arun
富含酪氨酸和酪氨酸的肽之间的液-液相分离（LLPS）具有重要的生物学意义。为了理解与复杂凝聚非常相似的凝聚相中蛋白质之间的相互作用，我们在含有酪氨酸（pY）和精氨酸（pR）的低聚物之间进行了多次伞形计算。我们发现pR-pY络合是能量驱动的。对单体的代谢动力学模拟表明，这种络合能与π-阳离子键的数目相关。对聚谷氨酸-pR二聚体之间的结合的自由能计算表明，这个过程和LLPS之间惊人的相似之处。这些计算表明，含有精氨酸和酪氨酸残基的蛋白质不经历络合，然后凝聚。相反，该机制类似于中性聚离子对的相分离。
Liquid–liquid phase separation (LLPS) between tyrosine- and arginine-rich peptides are of biological importance. To understand the interactions between proteins in the condensed phase in close analogy to complex coacervation, we run multiple umbrella calculations between oligomers containing tyrosine (pY) and arginine (pR). We find pR-pY complexation to be energetically driven. Metadynamics simulations on monomers suggest that this energy of complexation is correlated with the number of π-cation bonds. Free energy calculations for the binding between pairs of poly glutamate-pR dimers show striking similarities between this process and LLPS. These calculations suggest that proteins containing arginine and tyrosine residues do not undergo complexation followed by coacervation. The mechanism, rather, is akin to phase separation of neutral polyion pairs.