Setny Piotr, Borkowska Paulina, Worch Remigiusz
Centre of New Technologies, University of Warsaw, 2C Banacha St., Warsaw, Poland 02-097, Poland.
Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur St., Warsaw 02-093, Poland.
J Am Chem Soc. 2025 Apr 23;147(16):13385-13395. doi: 10.1021/jacs.4c18441. Epub 2025 Apr 11.
We propose an approach for determining the positioning of membrane-active peptides within a lipid bilayer. It is based on a combination of cryogenic electron microscopy (cryo-EM) with molecular dynamics (MD) simulations. Cryo-EM image intensity profiles across peptide-containing liposome membranes are analyzed by comparing them to synthetic images that are derived from MD trajectories of peptide-membrane systems representing different assumed binding modes. These simulated profiles serve as baseline models, which are then used to classify experimentally obtained images into respective categories. The approach was applied to influenza virus fusion peptides, providing evidence for predominantly transmembrane binding in pure POPC membranes and a transition toward surface-bound configurations upon the addition of cholesterol.
我们提出了一种确定膜活性肽在脂质双层中定位的方法。它基于低温电子显微镜（cryo-EM）与分子动力学（MD）模拟相结合。通过将含肽脂质体膜的低温电子显微镜图像强度分布与从代表不同假定结合模式的肽-膜系统的分子动力学轨迹得出的合成图像进行比较来分析。这些模拟分布作为基线模型，然后用于将实验获得的图像分类到各自的类别中。该方法应用于流感病毒融合肽，为在纯POPC膜中主要跨膜结合以及添加胆固醇后向表面结合构型的转变提供了证据。
