Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Av. do café, s/no. - Universidade de São Paulo, BR-14040-903 Ribeirão Preto, SP, Brazil; Laboratoire de Biochimie Theórique, UPR 9080 CNRS, Institut de Biologie Physico Chimique, Université Paris Diderot - Paris 7 et Université Sorbonne Paris Cité, 13 rue Pierre et Marie Curie, 75005 Paris, France.
Laboratoire de Biochimie Theórique, UPR 9080 CNRS, Institut de Biologie Physico Chimique, Université Paris Diderot - Paris 7 et Université Sorbonne Paris Cité, 13 rue Pierre et Marie Curie, 75005 Paris, France.
Biochem Biophys Res Commun. 2018 Mar 29;498(2):264-273. doi: 10.1016/j.bbrc.2017.07.027. Epub 2017 Jul 12.
Electrostatic interactions play a pivotal role in many (bio)molecular association processes. The molecular organization and function in biological systems are largely determined by these interactions from pure Coulombic contributions to more peculiar mesoscopic forces due to ion-ion correlation and proton fluctuations. The latter is a general electrostatic mechanism that gives attraction particularly at low electrolyte concentrations. This charge regulation mechanism due to titrating amino acid and nucleotides residues is discussed here in a purely electrostatic framework. By means of constant-pH Monte Carlo simulations based on a fast coarse-grained titration proton scheme, a new computer molecular model was devised to study protein-RNA interactions. The complexation between the RNA silencing suppressor p19 viral protein and the 19-bp small interfering RNA was investigated at different solution pH and salt conditions. The outcomes illustrate the importance of the charge regulation mechanism that enhances the association between these macromolecules in a similar way as observed for other protein-polyelectrolyte systems typically found in colloidal science. Due to the highly negative charge of RNA, the effect is more pronounced in this system as predicted by the Kirkwood-Shumaker theory. Our results contribute to the general physico-chemical understanding of macromolecular complexation and shed light on the extensive role of RNA in the cell's life.
静电相互作用在许多（生物）分子结合过程中起着关键作用。生物系统中的分子组织和功能在很大程度上取决于这些相互作用，从纯粹的库仑贡献到由于离子相关和质子波动引起的更特殊的介观力。后者是一种普遍的静电机制，特别是在低电解质浓度下会产生吸引力。本文在纯静电框架内讨论了由于滴定氨基酸和核苷酸残基而产生的这种电荷调节机制。通过基于快速粗粒化质子滴定方案的恒 pH 蒙特卡罗模拟，设计了一种新的计算机分子模型来研究蛋白质-RNA 相互作用。在不同的溶液 pH 和盐条件下研究了 RNA 沉默抑制子 p19 病毒蛋白与 19 个碱基的小干扰 RNA 之间的复合物形成。结果表明，电荷调节机制对于增强这些大分子之间的缔合非常重要，这种机制与胶体科学中通常发现的其他蛋白质-聚电解质系统中的观察结果类似。由于 RNA 的高度负电荷，根据 Kirkwood-Shumaker 理论预测，这种效应在该系统中更为明显。我们的结果有助于对大分子复合的一般物理化学理解，并阐明了 RNA 在细胞生命中的广泛作用。
