Chen Charles H, Wiedman Gregory, Khan Ayesha, Ulmschneider Martin B
Department of Materials Science and Engineering, Johns Hopkins University, Baltimore MD, USA.
Wolfson Centre for Age Related Disorders, Kings College London, London, UK.
Biochim Biophys Acta. 2014 Sep;1838(9):2243-9. doi: 10.1016/j.bbamem.2014.04.012. Epub 2014 Apr 21.
Unbiased molecular simulation is a powerful tool to study the atomic details driving functional structural changes or folding pathways of highly fluid systems, which present great challenges experimentally. Here we apply unbiased long-timescale molecular dynamics simulation to study the ab initio folding and partitioning of melittin, a template amphiphilic membrane active peptide. The simulations reveal that the peptide binds strongly to the lipid bilayer in an unstructured configuration. Interfacial folding results in a localized bilayer deformation. Akin to purely hydrophobic transmembrane segments the surface bound native helical conformer is highly resistant against thermal denaturation. Circular dichroism spectroscopy experiments confirm the strong binding and thermostability of the peptide. The study highlights the utility of molecular dynamics simulations for studying transient mechanisms in fluid lipid bilayer systems. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova.
无偏分子模拟是研究驱动高流动性系统功能结构变化或折叠途径的原子细节的有力工具，这些系统在实验上极具挑战性。在此，我们应用无偏长时间尺度分子动力学模拟来研究蜂毒素（一种典型的两亲性膜活性肽）的从头折叠和分配。模拟结果表明，该肽以无结构的构象强烈结合于脂质双层。界面折叠导致局部双层变形。与纯疏水跨膜片段类似，表面结合的天然螺旋构象对热变性具有高度抗性。圆二色光谱实验证实了该肽的强结合性和热稳定性。该研究突出了分子动力学模拟在研究流体脂质双层系统中瞬态机制方面的实用性。本文是名为“界面活性肽和蛋白质”特刊的一部分。客座编辑：威廉·C·温姆利和卡利娜·赫里斯托娃。
