Low temperature protein refolding suggested by molecular simulation
Low temperature protein refolding suggested by molecular simulation
复制标题
DOI：
10.1063/1.5128211
复制
发表时间：
2019-11-14
影响因子：
4.4
通讯作者：
Debenedetti, Pablo G.
中科院分区：
文献类型：
--
作者：
Kozuch, Daniel J.;Stillinger, Frank H.;Debenedetti, Pablo G.
关键生物材料（如蛋白质）的功能本质上与其结构有关，而这种结构又严重依赖于溶剂的性质，最常见的是水或稀水溶液。众所周知，水会表现出异常的性质，特别是在过冷温度下，很自然地会问这些性质如何影响蛋白质折叠的热力学。为了研究这个问题，我们使用分子模拟来探索模型微蛋白，色氨酸笼，低至70 K以下的溶剂在环境压力下的凝固点的行为。令人惊讶的是，我们发现，虽然预期的冷变性的蛋白质观察到在适度的过冷，进一步冷却到低于冰点超过55 K导致冷重折叠的蛋白质。结构和氢键分析表明，这种重折叠是由蛋白质的疏水核心的去溶剂化驱动的，可能与在该温度下密度的显著降低有关。除了他们的内在的基本利益，这些结果有影响的冷冻显微镜和冷冻保存，生物材料往往是短暂的受到这些极端条件。
The function of critical biological materials, such as proteins, is intrinsically tied to their structure, and this structure is in turn heavily dependent on the properties of the solvent, most commonly water or dilute aqueous solutions. As water is known to exhibit anomalous properties, especially at supercooled temperatures, it is natural to ask how these properties might impact the thermodynamics of protein folding. To investigate this question, we use molecular simulation to explore the behavior of a model miniprotein, Trp-cage, as low as 70 K below the freezing point of the solvent at ambient pressure. Surprisingly, we find that while the expected cold denaturation of the protein is observed at moderate supercooling, further cooling to more than 55 K below the freezing point leads to cold refolding of the protein. Structural and hydrogen bonding analysis suggests that this refolding is driven by the desolvation of the protein's hydrophobic core, likely related to the pronounced decrease in density at this temperature. Beyond their intrinsic fundamental interest, these results have implications for cryomicroscopy and cryopreservation, where biological materials are often transiently subjected to these extreme conditions.