Vestergaard Mikkel, Kraft Johan F, Vosegaard Thomas, Thøgersen Lea, Schiøtt Birgit
Center for Insoluble Protein Structures (inSPIN), Interdisciplinary Nanoscience Center (iNANO), and Department of Chemistry, Aarhus University , Langelandsgade 140, DK-8000 Aarhus C, Denmark.
Danish Center for Ultrahigh-Field NMR Spectroscopy and Center for Insoluble Protein Structures (inSPIN), Interdisciplinary Nanoscience Center (iNANO) and Department of Chemistry, Aarhus University , Gustav Wieds Vej 14, DK-8000 Aarhus C, Denmark.
J Phys Chem B. 2015 Dec 31;119(52):15831-43. doi: 10.1021/acs.jpcb.5b08463. Epub 2015 Dec 17.
The increased interest in studying membrane proteins has led to the development of new membrane mimics such as bicelles and nanodiscs. However, only limited knowledge is available of how these membrane mimics are affected by embedded proteins and how well they mimic a lipid bilayer. Herein, we present molecular dynamics simulations to elucidate structural and dynamic properties of small bicelles and compare them to a large alignable bicelle, a small nanodisc, and a lipid bilayer. Properties such as lipid packing and properties related to embedding both an α-helical peptide and a transmembrane protein are investigated. The small bicelles are found to be very dynamic and mainly assume a prolate shape substantiating that small bicelles cannot be regarded as well-defined disclike structures. However, addition of a peptide results in an increased tendency to form disc-shaped bicelles. The small bicelles and the nanodiscs show increased peptide solvation and difference in peptide orientation compared to embedding in a bilayer. The large bicelle imitated a bilayer well with respect to both curvature and peptide solvation, although peripheral binding of short tailed lipids to the embedded proteins is observed, which could hinder ligand binding or multimer formation.
对膜蛋白研究兴趣的增加促使了新型膜模拟物的开发，如双分子层微囊和纳米盘。然而，关于这些膜模拟物如何受到嵌入蛋白的影响以及它们对脂质双层的模拟效果如何，目前的了解还很有限。在此，我们进行了分子动力学模拟，以阐明小型双分子层微囊的结构和动力学特性，并将其与大型可排列双分子层微囊、小型纳米盘和脂质双层进行比较。我们研究了脂质堆积以及与嵌入α-螺旋肽和跨膜蛋白相关的特性。结果发现，小型双分子层微囊非常动态，主要呈现出长椭球形，这证实了小型双分子层微囊不能被视为明确的盘状结构。然而，添加肽会增加形成盘状双分子层微囊的趋势。与嵌入双层相比，小型双分子层微囊和纳米盘表现出肽溶剂化增加以及肽取向的差异。大型双分子层微囊在曲率和肽溶剂化方面都很好地模拟了双层，尽管观察到短尾脂质与嵌入蛋白的外周结合，这可能会阻碍配体结合或多聚体形成。
