论文标题
周围膜蛋白与脂质的特定相互作用：分子模拟可以显示什么？
Specific interactions of peripheral membrane proteins with lipids: what can molecular simulations show us?
论文作者
论文摘要
外围膜蛋白可以可逆性地结合到生物膜，以执行细胞信号，酶活性或膜重塑等功能。这些蛋白质及其脂质结合结构域的结构通常以可溶性形式溶解，有时在结合位点有脂质或脂质头组。为了提供周围膜蛋白与膜相互作用的详细分子视图，可以应用计算方法，例如分子动力学（MD）模拟。在这里，我们概述了最近尝试表征这些结合相互作用的尝试，重点是两种细胞内蛋白，例如结合结构域，以及细胞外蛋白，例如糖脂结合细菌毒素。我们比较了从模拟数据识别和分析脂质结合位点的方法。我们重点介绍了使用自由能计算的这些相互作用的最新工作。我们描述了方法论和计算能力的改进将如何帮助MD模拟将来继续为这一领域做出贡献。
Peripheral membrane proteins can reversibly and specifically bind to biological membranes to carry out functions such as cell signalling, enzymatic activity, or membrane remodelling. Structures of these proteins and of their lipid-binding domains are typically solved in a soluble form, sometimes with a lipid or lipid headgroup at the binding site. To provide a detailed molecular view of peripheral membrane protein interactions with the membrane, computational methods such as molecular dynamics (MD) simulations can be applied. Here, we outline recent attempts to characterise these binding interactions, focusing on both intracellular proteins such as PIP-binding domains, and on extracellular proteins such as glycolipid-binding bacterial exotoxins. We compare methods to identify and analyse lipid binding sites from simulation data. We highlight recent work characterising the energetics of these interactions using free energy calculations. We describe how improvements in methodologies and computing power will help MD simulations to continue to contribute to this field in the future.
