期刊
ACS NANO
卷 9, 期 3, 页码 2600-2613出版社
AMER CHEMICAL SOC
DOI: 10.1021/nn506161j
关键词
nanoparticles; amyloid; fibrillogenesis; docking; molecular dynamics; nuclear magnetic resonance
类别
资金
- MIUR through PRIN [2012A7LMS3003]
- Italian Institute of Technology through Platform Computations and Seed project MOPROSURF-MOdeling PROtein SURFace interactions
- Oak Ridge National Laboratory by the Scientific User Facilities Division, Office of Basic Energy Sciences, U.S. Department of Energy [CNMS2013-064]
- Office of Science of the U.S. Department of Energy [DE-AC02-05CH11231]
Nanoparticles (NPs) are known to exhibit distinct physical and chemical properties compared with the same materials in bulk form. NPs have been repeatedly, reported to interact With proteins, and this interaction can be exploited to affect processes undergone by proteins, such as fibrillogenesis. Fibrillation is common to many proteins, and in living organisms, it causes tissue-specific or systemic amyloid diseases. The nature of NPs and their surface chemistry is crucial in assessing their affinity for proteins and their effects on them. Here we present the first detailed structural characterization and molecular mechanics model of the interaction between a fibrillogenic protein, beta(2)-microglobulin, and a NP, 5 nm hydrophilic citrate-capped gold nanoparticles. NMR measurements and simulations at multiple levels (enhanced sampling molecular dynamics, Brownian dynamics, and Poisson Boltzmann electrostatics) explain the origin of the observed protein perturbations mostly localized at the amino-terminal region. Experiments show that the protein NP interaction is weak in the physiological-like, conditions and do not induce protein fibrillation. Simulations reproduce these findings and reveal instead the role of the citrate in destabilizing the lower protonated form of beta(2)-microglobulin. The results offer possible strategies for controlling the desired effect of NPs on the conformational changes of the proteins, which have significant roles in the fibrillation process.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据