Molecular Dynamics Simulations of Low-Ordered Alzheimer 尾-Amyloid Oligomers from Dimer to Hexamer on Self-Assembled Monolayers

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• 作者：Jun Zhao ; Qiuming Wang ; Guizhao Liang ; Jie Zheng
• 刊名：Langmuir
• 出版年：2011
• 出版时间：December 20, 2011
• 年：2011
• 卷：27
• 期：24
• 页码：14876-14887
• 全文大小：1511K
• 年卷期：v.27,no.24(December 20, 2011)
• ISSN：1520-5827

文摘

Accumulation of small soluble oligomers of amyloid-尾 (A尾) in the human brain is thought to play an important pathological role in Alzheimer鈥檚 disease. The interaction of these A尾 oligomers with cell membrane and other artificial surfaces is important for the understanding of A尾 aggregation and toxicity mechanisms. Here, we present a series of exploratory molecular dynamics (MD) simulations to study the early adsorption and conformational change of A尾 oligomers from dimer to hexamer on three different self-assembled monolayers (SAMs) terminated with CH₃, OH, and COOH groups. Within the time scale of MD simulations, the conformation, orientation, and adsorption of A尾 oligomers on the SAMs is determined by complex interplay among the size of A尾 oligomers, the surface chemistry of the SAMs, and the structure and dynamics of interfacial waters. Energetic analysis of A尾 adsorption on the SAMs reveals that A尾 adsorption on the SAMs is a net outcome of different competitions between dominant hydrophobic A尾鈥揅H₃-SAM interactions and weak CH₃-SAM鈥搘ater interactions, between dominant electrostatic A尾鈥揅OOH-SAM interactions and strong COOH-SAM鈥搘ater interactions, and between comparable hydrophobic and electrostatic A尾鈥揙H-SAM interactions and strong OH-SAM鈥搘ater interactions. Atomic force microscopy images also confirm that all of three SAMs can induce the adsorption and polymerization of A尾 oligomers. Structural analysis of A尾 oligomers on the SAMs shows a dramatic increase in structural stability and 尾-sheet content from dimer to trimer, suggesting that A尾 trimer could act as seeds for A尾 polymerization on the SAMs. This work provides atomic-level understanding of A尾 peptides at interface.