Biophys J. 2012 Dec 19;103(12):L47-9. doi: 10.1016/j.bpj.2012.11.009. Epub 2012 Dec 18.
Amyloid beta (Aβ) peptide plays an important role in Alzheimer's disease. A number of mutations in the Aβ sequence lead to familial Alzheimer's disease, congophilic amyloid angiopathy, or hereditary cerebral hemorrhage with amyloid. Using molecular dynamics simulations of ∼200 μs for each system, we characterize and contrast the consequences of four pathogenic mutations (Italian, Dutch, Arctic, and Iowa) for the structural ensemble of the Aβ monomer. The four familial mutations are found to have distinct consequences for the monomer structure.
淀粉样蛋白β(Aβ)肽在阿尔茨海默病中起重要作用。Aβ 序列中的许多突变导致家族性阿尔茨海默病、嗜刚果红淀粉样血管病或伴淀粉样的遗传性脑血性。通过对每个系统进行约 200 μs 的分子动力学模拟,我们对 Aβ 单体的结构整体的四个致病性突变(意大利、荷兰、北极和爱荷华)的后果进行了描述和对比。这四个家族性突变对单体结构有明显不同的影响。