Recent experiments suggested that ATP can effectively stabilize protein structure and inhibit protein aggregation when its concentration is less than 10 mM, which is significantly lower than cosolvent concentrations required in conventional mechanisms. The ultrahigh efficiency of ATP suggests a unique mechanism that is fundamentally different from previous models of cosolvents. In this work, we used molecular dynamics simulation and experiments to study the interactions of ATPs with three proteins: lysozyme, ubiquitin, and malate dehydrogenase. ATP tends to bind to the surface regions with high flexibility and high degree of hydration. These regions are also vulnerable to thermal perturbations. The bound ATPs further assemble into ATP clusters mediated by Mg²⁺ and Na⁺ ions. More interestingly, in Mg²⁺-free ATP solution, Na⁺ at higher concentration (150 mM under physiological conditions) can similarly mediate the formation of the ATP cluster on protein. The ATP cluster can effectively reduce the fluctuations of the vulnerable region and thus stabilize the protein against thermal perturbations. Both ATP binding and the considerable improvement of thermal stability of ATP-bound protein were verified by experiments.

中文翻译：

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ATP可通过独特机制有效稳定蛋白质

最近的实验表明，当 ATP 浓度低于 10 mM 时，可以有效地稳定蛋白质结构并抑制蛋白质聚集，这显着低于常规机制所需的助溶剂浓度。ATP 的超高效率表明了一种独特的机制，它与以前的助溶剂模型有着根本的不同。在这项工作中，我们使用分子动力学模拟和实验来研究 ATP 与三种蛋白质的相互作用：溶菌酶、泛素和苹果酸脱氢酶。ATP 倾向于以高灵活性和高水合度结合到表面区域。这些区域也容易受到热扰动的影响。结合的 ATP 进一步组装成由 Mg ²⁺和 Na ⁺介导的 ATP 簇离子。更有趣的是，在不含 Mg ^{2+ 的}ATP 溶液中，较高浓度的Na ⁺（生理条件下为 150 mM）可以类似地介导蛋白质上 ATP 簇的形成。ATP 簇可以有效减少脆弱区域的波动，从而稳定蛋白质免受热扰动。实验证实了 ATP 结合和 ATP 结合蛋白的热稳定性的显着改善。