富勒烯与β淀粉样肽低聚体结合的分子动力学模拟

本文通过分子动力学模拟研究富勒烯在Aβ42 低聚体表面的结合过程. 在结合过程中,C₆₀在Aβ表面经历一系列尝试过程,最终找到某个稳定的结合位点. 根据结合的残基不同,这些结合位点可以分为六类,其中核心疏水区域（CHC）位点（¹⁷LVFFA²¹）及Turn 27-31 位点（²⁷NKGAI³¹）具有最强的结合稳定性. 二者的结合主要通过范德华作用稳定,而溶剂化效应则起相反作用. 在这六类位点中的两个位点,观察到C₆₀会对Aβ二级结构起破坏作用. 其一位于核心疏水区域,C₆₀有挤入多肽β片层中间的趋势;另外一位点位于N端,C₆₀能够破坏外侧Aβ的3-5 号残基的主链氢键,瓦解其末端的β片结构. 这两个过程对理解富勒烯抑制Aβ聚集的微观机制提供了帮助. 此外,在Turn 27-31 位点以及Y10-H14 位点,发现了富勒烯与Aβ纤维样聚集体结合的沟槽滚动机制,即富勒烯能够在淀粉样低聚体表面形成的特定沟槽内滚动. 这一特征有助于预测富勒烯在其它淀粉样多肽表面的结合位点及结合行为.     

Amyloid-β peptide aggregation and the influence of carbon nanoparticles

Soluble peptides or proteins can self-aggregate into insoluble, ordered amyloid fibrils under appropriate conditions.These amyloid aggregates are the hallmarks of several human diseases ranging from neurodegenerative disorders to systemic amyloidoses. In this review, we first introduce the common structural features of amyloid fibrils and the amyloid fibrillation kinetics determined from experimental studies. Then, we discuss the structural models of Alzheimer's amyloid-β(Aβ) fibrils derived from solid-state nuclear magnetic resonance spectroscopy. On the computational side, molecular dynamics simulations can provide atomic details of structures and the underlying oligomerization mechanisms. We finally summarize recent progress in atomistic simulation studies on the oligomerization of Aβ(including full-length Aβ and its fragments) and the influence of carbon nanoparticles.