College of Physics Science and Technology, Yangzhou University, Jiangsu 225009, China.
Key Laboratory of Polar Materials and Devices, Ministry of Education, College of Physics and Electronic Science, East China Normal University, Shanghai 200062, China.
Phys Rev E. 2020 Feb;101(2-1):022410. doi: 10.1103/PhysRevE.101.022410.
Magnesium (Mg^{2+}) and calcium (Ca^{2+}) are of essential importance in biological activity, but the molecular understanding of their selectivity is still lacking. Here, based on density functional theory calculations and ab initio molecular dynamics simulations, we show that Mg^{2+} binds more tightly to phosphotyrosine (pTyr) and stabilizes the conformation of pTyr, while Ca^{2+} binds more flexibly to pTyr with less structural stability. The key for the selectivity is attributed to the cation-π interactions between the hydrated cations and the aromatic ring together with the synergic interaction between the cations and the side groups in pTyr to form a cation-binding pocket structure, which we refer as side-group-synergetic hydrated cation-π interaction. The existence and relative strength of the cation-π interactions in the pocket structures as well as their structural stability have been demonstrated experimentally with ultraviolet (UV) absorption spectra and ^{1}H NMR spectra. The findings offer insight into understanding the selectivity of Mg^{2+} and Ca^{2+} in a variety of biochemical and physiological essential processes.
镁（Mg^{2+}）和钙（Ca^{2+}）在生物活性中具有至关重要的作用，但对它们选择性的分子理解仍有所欠缺。在这里，我们基于密度泛函理论计算和从头分子动力学模拟，表明 Mg^{2+}与磷酸酪氨酸（pTyr）结合更紧密，并稳定 pTyr 的构象，而 Ca^{2+}与 pTyr 结合更灵活，结构稳定性较低。选择性的关键归因于水合阳离子与芳环之间的阳离子-π 相互作用以及阳离子与 pTyr 侧基之间的协同相互作用，形成阳离子结合口袋结构，我们称之为侧基协同水合阳离子-π 相互作用。口袋结构中阳离子-π 相互作用的存在及其相对强度以及它们的结构稳定性已经通过紫外（UV）吸收光谱和 ^{1}H NMR 光谱得到实验验证。这些发现为理解 Mg^{2+}和 Ca^{2+}在各种生化和生理必需过程中的选择性提供了深入了解。
