溶剂对Aβ单体从淀粉样纤维表面解离的影响

Effects of solvents on dissociation of Aβ monomer from amyloid fibril

通过采用分子动力学模拟的方法,研究了溶剂对Aβ单体从淀粉样纤维表面解离过程的影响.淀粉样纤维内的Aβ单体在结构上由一个柔性的环连接两个β股构成.在450K的高温下,Aβ单体的解离从N端β1股的破裂开始,而C端β2股在整个模拟过程中的结构基本保持稳定,研究结果表明解离过程主要归因于淀粉样纤维C端存在较强的疏水相互作用;尿素分子能够通过破坏骨架间的氢键相互作用从而加速纤维单体的构象变化;研究结果同时表明尿素分子能够增强带电残基间的静电作用从而延缓纤维单体的解离.研究结果有助于阐明溶剂在Aβ解离过程中的分子机制.

Using all-atom molecular dynamics simulation, we studied the effects of solvents on dissociation of Aβ monomer from the amyloid fibril. The Aβ monomer in fibril mainly is composed of two β-strands, and a long flexible loop connects the two β-strands. At high temperature, dissociation started with the β1-strand of N-terminal, the conformation of C-terminal remains stability throughout simulation at 450 K. The results indicate that process of dissociation should partly be attributed to the N-terminal hydrophobic interaction of Aβ;the aqueous urea can accelerate the process of dissociation and unfolding of edge peptide by breaking backbone-backbone hydrogen bonds interaction. The results also show that the electrostatic interaction in amyloid fibril has little effect on the dissociation process of temperature-induced fibril monomer. We believe that the results will help decipher the molecular mechanism(s) of solvent effects on Aβ.