Singh Aditya N, Yethiraj Arun
Theoretical Chemistry Institute and Department of Chemistry, 1101 University Avenue, University of Wisconsin-Madison, Madison, Wisconsin 53703, United States.
J Phys Chem B. 2021 Apr 1;125(12):3023-3031. doi: 10.1021/acs.jpcb.0c07349. Epub 2021 Mar 18.
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.
富含酪氨酸和精氨酸的肽之间的液-液相分离（LLPS）具有生物学重要性。为了类似于复合凝聚那样深入理解凝聚相中蛋白质之间的相互作用，我们对含酪氨酸（pY）和精氨酸（pR）的寡聚物进行了多次伞形计算。我们发现pR-pY络合是由能量驱动的。对单体的元动力学模拟表明，这种络合能量与π-阳离子键的数量相关。聚谷氨酸-pR二聚体对之间结合的自由能计算表明，这一过程与LLPS之间存在显著相似性。这些计算表明，含有精氨酸和酪氨酸残基的蛋白质不会先发生络合然后凝聚。相反，其机制类似于中性聚离子对的相分离。
