Institute for Molecular Science, National Institutes of Natural Sciences, Okazaki 444-8787, Aichi, Japan.
Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, Okazaki 444-8787, Aichi, Japan.
Int J Mol Sci. 2021 Feb 13;22(4):1859. doi: 10.3390/ijms22041859.
Aggregates of amyloid-β (Aβ) peptides are known to be related to Alzheimer's disease. Their aggregation is enhanced at hydrophilic-hydrophobic interfaces, such as a cell membrane surface and air-water interface, and is inhibited by polyphenols, such as myricetin and rosmarinic acid. We review molecular dynamics (MD) simulation approaches of a full-length Aβ peptide, Aβ40, and Aβ(16-22) fragments in these environments. Since these peptides have both hydrophilic and hydrophobic amino acid residues, they tend to exist at the interfaces. The high concentration of the peptides accelerates the aggregation there. In addition, Aβ40 forms a β-hairpin structure, and this structure accelerates the aggregation. We also describe the inhibition mechanism of the Aβ(16-22) aggregation by polyphenols. The aggregation of Aβ(16-22) fragments is caused mainly by the electrostatic attraction between charged amino acid residues known as Lys16 and Glu22. Since polyphenols form hydrogen bonds between their hydroxy and carboxyl groups and these charged amino acid residues, they inhibit the aggregation.
淀粉样蛋白-β (Aβ) 肽的聚集体已知与阿尔茨海默病有关。它们在亲水-疏水界面（如细胞膜表面和气-水界面）上的聚集得到增强，并受到多酚如杨梅素和迷迭香酸的抑制。我们回顾了全长 Aβ 肽 Aβ40 和 Aβ(16-22) 片段在这些环境中的分子动力学 (MD) 模拟方法。由于这些肽既有亲水氨基酸残基又有疏水氨基酸残基，它们往往存在于界面上。高浓度的肽加速了在这些界面处的聚集。此外，Aβ40 形成 β-发夹结构，该结构加速了聚集。我们还描述了多酚对 Aβ(16-22) 聚集的抑制机制。Aβ(16-22) 片段的聚集主要是由带电荷的氨基酸残基 Lys16 和 Glu22 之间的静电吸引引起的。由于多酚在其羟基和羧基与这些带电荷的氨基酸残基之间形成氢键，因此它们抑制了聚集。
