淀粉样肽的错误折叠和聚集（或纤维化）与阿兹海默症等多种淀粉样变性病密切相关，人们一直在寻找能有效抑制淀粉样肽聚集的抑制剂。由于纳米颗粒较短肽抑制剂能更容易地通过血脑屏障进入人体，纳米颗粒调控淀粉样肽聚集的研究越来越受到人们的关注。然而，由于二者相互作用的复杂性，纳米颗粒抑制或促进淀粉样肽纤维化的微观机理尚不清楚。本项目拟采用分子动力学、副本交换分子动力学模拟、和实验方法，以碳纳米颗粒（包括碳纳米管和富勒烯）和表面修饰不同基团的碳纳米颗粒与阿兹海默症beta淀粉样肽及其不同氨基酸片段的相互作用为主要研究内容，通过分析纳米颗粒的大小、形状、浓度、亲疏水性、带电性等对淀粉样肽聚集的影响，揭示淀粉样肽的构象动力学、聚集体结构、聚集路径、聚集自由能面及与纳米颗粒作用的关键氨基酸，找出影响聚集的主要因素，阐明纳米颗粒调控淀粉样肽聚集的物理机制。此研究将为开发治疗淀粉样变性病相关药物提供新的思路。

Protein/peptide misfolding and aggregation are associated with many amyloidosis such as Alzheimer disease. The inhibition of amyloid formation has been considered as the primary therapeutic strategy for the amyloidosis diseases. In recent years, nanoparticles have been received considerable attention due to their potential applications in the field of nanomedicine. Experimental studies have shown that nanoparticles inhibit/promote amyloid formation by increasing/decreasing the nucleation process. However, the details of molecular interactions between amyloid peptide and nanoparticle are still not well understood. In this proposal, we investigate the detailed interactions of different nanoparticles (including carbon nanoparticles and covalently functionalized carbon-nanoparticles) with Alzheimer's amyloid beta peptide as well as its different fragments by performing molecular dynamics and replica-exchange molecular dynamics simulations in explicit solvent comined with experimental methods. We will examine the impact of hydrophobicity, hydrophilicity, size, shape, and concentration of nanoparticles on the dynamics and thermodynamics of amyloid peptide oligomerization. The structure, aggregation path, and the free energy surface of amyloid ologomers will be identified. The aim of this project is to reveal the molecular mechanism of nanoparticle-mediated amyloid peptide aggregation. The results and the findings would provide new clues for the development of drug candidates against amyloidosis.