质子化作用对Aβ1—16单体结构特征和聚集机理的影响

利用副本交换分子动力学模拟研究了Aβ肽(β-Amyloid peptide)N末端部分Aβ1—16单体在pH为7.0,6.3及5.5水溶液状态下的结构特征以及聚集机理.通过建模确定了不同pH状态下Aβ1—16肽链的质子化位置(残基),通过模拟比较了不同酸性溶液状态下Aβ1—16单体的结构和能量变化.结果表明,在中性条件下,Aβ1—16单体保持自由卷曲结构,而在酸性状态下,其结构由最初的无序状态向有序状态转变,模拟过程中β-折叠结构会间歇性产生,预示着单体可以发生自聚集现象.本文所得结论,即酸性状态下的Aβ1—16单体质子化位及模拟过程中的结构变化,可用于酸性状态下金属离子与Aβ1—16可能的残基结合位及结合数量的有效预测和评估.

Effect of Protonation on Structural Characteristics and Aggregation Mechanisms of β-Amyloid(1—16) Peptide

Structural characteristics and aggregation mechanisms of Aβ1—16 fragment under different conditions of pH=7.0, 6.3 and 5.5 were studied by replica exchange molecular dynamics(REMD). The results show that protonated residues and number of Aβ1—16 depend on the difference of pH. Structural changes indicate that Aβ1—16 has a transitional trend from the disordered state to the ordered one along with the increase of acidic concentration. β-Sheet intermittently appears in acidic conditions during the simulations, implying that Aβ1—16 tends to self-aggregation in such case. The protonated positions and structural changes of Aβ1—16 monomer depicted in the present work can be employed to predict and assess the potential binding positions and coordination numbers for a transition metal ion to approach the monomer.