It has long been recognized that liquid interfaces, such as the air–water interface (AWI), can enhance the formation of protein fibrils. This makes liquid interfaces attractive templates for fibril formation but fully realizing this requires knowledge of protein behavior at interfaces, which is currently lacking. To address this, molecular dynamics simulation is used to investigate fragments of amyloid beta, a model fibril forming protein, at the air–water interface. At the air–water interface, the enrichment of aggregation-prone helical conformations provides a mechanism for the enhancement of fibrillation at interfaces. The conformational ensemble at the air–water interface was also considerably reduced compared to bulk solution due to the tendency of hydrophobic side chains partitioning into the air restricting the range of conformations. Little overlap between the conformational ensembles at the AWI and in the bulk solution was found, suggesting that AWI induces the formation of a different set of structures compared to bulk solution. The smaller A$\beta$(16–22) and A$\beta$(25–35) fragments show an increase in the propensity for an ordered secondary structure at the air–water interface but with a increased propensity for turn over other motifs, illustrating the importance of intra-protein interactions for stabilizing helical and extended conformations.

中文翻译：

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气水界面对淀粉样蛋白β构象的影响

人们早就认识到，液体界面，如空气-水界面 (AWI)，可以促进蛋白质原纤维的形成。这使得液体界面成为原纤维形成的有吸引力的模板，但要完全意识到这一点，需要了解界面上的蛋白质行为，而这目前是缺乏的。为了解决这个问题，我们使用分子动力学模拟来研究空气 - 水界面处的淀粉样蛋白 β（一种模型原纤维形成蛋白）的片段。在空气-水界面，易于聚集的螺旋构象的富集提供了增强界面原纤化的机制。由于疏水侧链分配到空气中限制了构象范围的趋势，与本体溶液相比，空气-水界面的构象集合也大大减少。发现 AWI 和本体溶液中的构象集合之间几乎没有重叠，这表明与本体溶液相比，AWI 诱导了一组不同结构的形成。较小的 A$\beta$(16–22) 和 A$\beta$(25-35) 片段显示在空气 - 水界面有序二级结构的倾向增加，但其他基序的倾向增加，说明蛋白质内相互作用对稳定螺旋和扩展构象的重要性。