Mechanism of protein-RNA recognition: analysis based on the statistical mechanics of hydration.
Mechanism of protein-RNA recognition: analysis based on the statistical mechanics of hydration.
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DOI：
10.1039/c8cp00155c
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发表时间：
2018-04
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影响因子：
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通讯作者：
Tomohiko Hayashi;Tomoaki Matsuda;T. Nagata;M. Katahira;M. Kinoshita
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作者：
Tomohiko Hayashi;Tomoaki Matsuda;T. Nagata;M. Katahira;M. Kinoshita
我们使用生物分子的全原子模型、水的分子模型和目前最可靠的统计力学方法，以Rbd1-r(GUAGU)结合为例进行研究。Rbd1是哺乳动物Musashi1(Msi1)的RNA结合域之一，r(GUAGU)包含对Msi1的最小识别序列，r(GUAG)。我们发现，这种结合是由整个体系中水的构型熵的大幅增加所驱动的。它大于Rbd1和r(GUAGU)的构象熵损失之和。Rbd1-r(GUAGU)结合时相互作用能的降低在很大程度上被Rbd1-水、r(GUAGU)-水和水-水相互作用能的增加所抵消。我们将这种增加称为“能量脱水”。降幅大于范德瓦尔斯分量的升幅，而静电分量的升幅正好相反。我们给出了一个新的原因，经验性已知的事实，即具有带正电荷和平坦部分的侧链的蛋白质残基经常出现在蛋白质-RNA结合界面中。然后给出了蛋白质-RNA结合机制的物理图。为了获得足够大的水熵增益，需要利用平坦部分(蛋白质的芳环和RNA的碱基)的堆积和夹杂作为基本基序，在原子水平上构建形状互补。为了补偿静电能量脱水，电荷互补在结合界面内变得至关重要。我们论证了RNA识别基序(RRM)是最普遍存在的RNA结合域的原因。
We investigate the RBD1-r(GUAGU) binding as a case study using all-atom models for the biomolecules, molecular models for water, and the currently most reliable statistical-mechanical method. RBD1 is one of the RNA-binding domains of mammalian Musashi1 (Msi1), and r(GUAGU) contains the minimum recognition sequence for Msi1, r(GUAG). We show that the binding is driven by a large gain of configurational entropy of water in the entire system. It is larger than the sum of conformational-entropy losses for RBD1 and r(GUAGU). The decrease in RBD1-r(GUAGU) interaction energy upon binding is largely cancelled out by the increase in the sum of RBD1-water, r(GUAGU)-water, and water-water interaction energies. We refer to this increase as "energetic dehydration". The decrease is larger than the increase for the van der Waals component, whereas the opposite is true for the electrostatic component. We give a novel reason for the empirically known fact that protein residues possessing side chains with positive charges and with flat moieties frequently appear within protein-RNA binding interfaces. A physical picture of the general protein-RNA binding mechanism is then presented. To achieve a sufficiently large water-entropy gain, shape complementarity at the atomic level needs to be constructed by utilizing the stacking and sandwiching of flat moieties (aromatic rings of the protein and nucleobases of RNA) as fundamental motifs. To compensate for electrostatic energetic dehydration, charge complementarity becomes crucial within the binding interface. We argue the reason why the RNA recognition motif (RRM) is the most ubiquitous RNA binding domain.