Magnesium $\left(\mathrm{M}{\mathrm{g}}^{2+}\right)$ and calcium $\left(\mathrm{C}{\mathrm{a}}^{2+}\right)$ 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 $\mathrm{M}{\mathrm{g}}^{2+}$ binds more tightly to phosphotyrosine (pTyr) and stabilizes the conformation of pTyr, while $\mathrm{C}{\mathrm{a}}^{2+}$ 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 ${}^1\mathrm{H}$ NMR spectra. The findings offer insight into understanding the selectivity of $\mathrm{M}{\mathrm{g}}^{2+}$ and $\mathrm{C}{\mathrm{a}}^{2+}$ in a variety of biochemical and physiological essential processes.

中文翻译：

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磷酸酪氨酸阳离子结合口袋结构中镁和钙的选择性机理

镁 $（\mathrm{中号}{\mathrm{G}}^{2+}）$ 和钙 $（\mathrm{C}{\mathrm{一种}}^{2+}）$对生物活性至关重要，但仍缺乏对其选择性的分子理解。在此，基于密度泛函理论计算和从头算分子动力学模拟，我们证明了$\mathrm{中号}{\mathrm{G}}^{2+}$ 与磷酸酪氨酸（pTyr）更紧密地结合并稳定pTyr的构象，而 $\mathrm{C}{\mathrm{一种}}^{2+}$与pTyr更灵活地结合，结构稳定性更低。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中侧基之间的协同相互作用，从而形成阳离子结合袋结构，我们将其称为侧基-基团协同水合阳离子-π相互作用。通过紫外（UV）吸收光谱和红外光谱实验证明了口袋结构中阳离子-π相互作用的存在和相对强度及其结构稳定性。${}^{\mathrm{1个}}\mathrm{H}$NMR光谱。这些发现提供了对理解选择性的洞察力。$\mathrm{中号}{\mathrm{G}}^{2+}$ 和 $\mathrm{C}{\mathrm{一种}}^{2+}$ 处于各种生化和生理过程中。