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首页> 外文期刊>RSC Advances >Modelling of interactions between Aβ(25–35) peptide and phospholipid bilayers: effects of cholesterol and lipid saturation
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Modelling of interactions between Aβ(25–35) peptide and phospholipid bilayers: effects of cholesterol and lipid saturation

机译：Aβ（25-35）肽和磷脂双层相互作用的建模：胆固醇和脂质饱和的影响

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摘要

Aggregation of amyloid beta (Aβ) peptides in neuronal membranes is a known promoter of Alzheimer’s disease. To gain insight into the molecular details of Aβ peptide aggregation and its effect on model neuronal membranes, we carried out molecular dynamics simulations of the Aβ(25–35) fragment of the amyloid precursor protein in phospholipid bilayers composed of either fully saturated or highly unsaturated lipids, in the presence or absence of cholesterol. It was found that the peptide does not penetrate through any of the considered membranes, but can reside in the headgroup region and upper part of the lipid tails showing a clear preference to a polyunsaturated cholesterol-free membrane. Due to the ordering and condensing effect upon addition of cholesterol, membranes become more rigid facilitating peptide aggregation on the surface. Except for the case of the cholesterol-free saturated lipid bilayer, the peptides have a small effect on the membrane structure and ordering. It was also found that the most “active” amino-acid for peptide–lipid and peptide–cholesterol interaction is methionine-35, followed by asparagine-27 and serine-26, which form hydrogen bonds between peptides and polar atoms of lipid headgroups. These amino acids are also primarily responsible for peptide aggregation. This work will be relevant for designing strategies to develop drugs to combat Alzheimer’s disease.
机译：神经元膜中淀粉样蛋白β（Aβ）肽的聚集是阿尔茨海默病的已知启动子。为了深入了解Aβ肽聚集的分子细节及其对模型神经元膜的影响，我们对由完全饱和或高度不饱和的磷脂双层中的淀粉样蛋白前体蛋白的Aβ（25-35）片段进行了分子动力学模拟脂质，在存在或不存在胆固醇中。发现肽不渗透到任何所考虑的膜中，而是可以存在于头部组和脂质尾的上部，显示出对多不饱和胆固醇膜的清晰偏好。由于在加入胆固醇后的排序和冷凝效果，膜变得更加刚性促进表面的肽聚集。除了无胆固醇无饱和脂质双层的情况外，肽对膜结构的效果很小并排序。还发现肽 - 脂质和肽 - 胆固醇相互作用的最“活性”氨基酸是甲硫氨酸-35，然后是浅冬酰胺-27和丝氨酸-26，其在肽和极性原子之间形成脂质头组之间的氢键。这些氨基酸也主要负责肽聚集。这项工作将与设计策略，以发展毒品，以打击阿尔茨海默病。

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