Mechanical processes are involved at many stages of the development of living cells, and often external forces applied to a biomolecule result in its unfolding. Although our knowledge of the unfolding mechanisms and the magnitude of the forces involved has evolved, the role that water molecules play in the mechanical unfolding of biomolecules has not yet been fully elucidated. To this end, we investigated with steered molecular dynamics simulations the mechanical unfolding of dystrophin's spectrin repeat 1 and related the changes in the protein's structure to the ordering of the surrounding water molecules. Our results indicate that upon mechanically induced unfolding of the protein, the solvent molecules become more ordered and increase their average number of hydrogen bonds. In addition, the unfolded structures originating from mechanical pulling expose an increasing amount of the hydrophobic residues to the solvent molecules, and the uncoiled regions adapt a convex surface with a small radius of curvature. As a result, the solvent molecules reorganize around the protein's small protrusions in structurally ordered waters that are characteristic of the so-called "small-molecule regime," which allows water to maintain a high hydrogen bond count at the expense of an increased structural order. We also determined that the response of water to structural changes in the protein is localized to the specific regions of the protein that undergo unfolding. These results indicate that water plays an important role in the mechanically induced unfolding of biomolecules. Our findings may prove relevant to the ever-growing interest in understanding macromolecular crowding in living cells and their effects on protein folding, and suggest that the hydration layer may be exploited as a means for short-range allosteric communication.

中文翻译：

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Spectrin 重复的机械展开诱导水分子排序

机械过程涉及活细胞发育的许多阶段，通常施加到生物分子上的外力会导致其展开。尽管我们对展开机制和所涉及力的大小的了解已经发展，但水分子在生物分子机械展开中所起的作用尚未完全阐明。为此，我们通过受控分子动力学模拟研究了抗肌萎缩蛋白的血影蛋白重复序列​​ 1 的机械展开，并将蛋白质结构的变化与周围水分子的排序相关联。我们的结果表明，在蛋白质的机械诱导解折叠后，溶剂分子变得更加有序并增加了它们的平均氢键数。此外，源自机械牵引的未折叠结构将越来越多的疏水残基暴露于溶剂分子中，而未卷曲的区域则采用具有小曲率半径的凸面。结果，溶剂分子在结构有序的水中围绕蛋白质的小突起重新组织，这是所谓的“小分子机制”的特征，它允许水以增加的结构顺序为代价保持高氢键数. 我们还确定水对蛋白质结构变化的反应局限于蛋白质的特定区域进行解折叠。这些结果表明水在机械诱导的生物分子展开中起着重要作用。