Campbell Oluwatoyin, Allsopp Robert, Klauda Jeffery B, Monje Viviana
Chemical and Biological Engineering Department, School of Engineering and Applied Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
Chemical and Biomolecular Engineering Department, A. James Clark School of Engineering, University of Maryland, College Park, MD, USA.
Methods Mol Biol. 2025;2888:281-303. doi: 10.1007/978-1-0716-4318-1_19.
All-atom molecular dynamics (AAMD) is a computational technique that predicts the movement of particles based on the intermolecular forces acting on the system. It enables the study of biological systems at atomic detail, complements observations from experiments, and can help the selection of experimental targets. Here, we describe the applications of MD simulations to study the interaction between peripheral membrane proteins and lipid bilayers. Specifically, we provide step-by-step instructions to set up MD simulations to study the binding and interaction of ALPS, the amphipathic helix of the lipid transport protein Osh4, and Thanatin, an antimicrobial peptide with model membranes. We describe examples of systems built with fully atomistic lipid tails and those truncated with the highly-mobile-membrane-mimetic method to enhance conformational sampling. We also comment on the importance of lipid diversity, molecular resolution, and best practices for constructing, running, and analyzing protein-lipid simulation systems. In this second edition, we include a brief discussion on alternative approaches and software to construct protein-membrane coordinate systems, as well as analysis tools and practices that have become relevant to examining protein-lipid interactions since the first edition of this chapter.
全原子分子动力学（AAMD）是一种计算技术，它基于作用于系统的分子间力来预测粒子的运动。它能够在原子层面研究生物系统，补充实验观察结果，并有助于选择实验靶点。在这里，我们描述了分子动力学模拟在研究外周膜蛋白与脂质双层之间相互作用方面的应用。具体而言，我们提供了逐步指导，以建立分子动力学模拟来研究脂质转运蛋白Osh4的两亲性螺旋ALPS与具有模型膜的抗菌肽Thanatin之间的结合和相互作用。我们描述了用全原子脂质尾部构建的系统以及用高流动性膜模拟方法截断的系统的示例，以增强构象采样。我们还评论了脂质多样性、分子分辨率的重要性，以及构建、运行和分析蛋白质-脂质模拟系统的最佳实践。在第二版中，我们简要讨论了构建蛋白质-膜坐标系的替代方法和软件，以及自本章第一版以来与研究蛋白质-脂质相互作用相关的分析工具和实践。
