Department of Chemistry, Umeå University, Umeå, Sweden.
J Membr Biol. 2021 Feb;254(1):51-64. doi: 10.1007/s00232-020-00165-8. Epub 2021 Jan 7.
Membrane proteins govern critical cellular processes and are central to human health and associated disease. Understanding of membrane protein function is obscured by the vast ranges of structural dynamics-both in the spatial and time regime-displayed in the protein and surrounding membrane. The membrane lipids have emerged as allosteric modulators of membrane protein function, which further adds to the complexity. In this review, we discuss several examples of membrane dependency. A particular focus is on how molecular dynamics (MD) simulation have aided to map membrane protein dynamics and how enhanced sampling methods can enable observing the otherwise inaccessible biological time scale. Also, time-resolved X-ray scattering in solution is highlighted as a powerful tool to track membrane protein dynamics, in particular when combined with MD simulation to identify transient intermediate states. Finally, we discuss future directions of how to further develop this promising approach to determine structural dynamics of both the protein and the surrounding lipids.
膜蛋白调控着关键的细胞过程，是人类健康和相关疾病的核心。由于蛋白质和周围膜显示出在空间和时间范围内的广泛结构动力学，膜蛋白功能的理解受到阻碍。膜脂已成为膜蛋白功能的变构调节剂，这进一步增加了复杂性。在这篇综述中，我们讨论了几个膜依赖性的例子。特别关注的是分子动力学（MD）模拟如何帮助绘制膜蛋白动力学图，以及增强采样方法如何能够观察到否则无法达到的生物时间尺度。此外，溶液中时分辨 X 射线散射被强调为跟踪膜蛋白动力学的有力工具，特别是当与 MD 模拟结合以识别瞬态中间状态时。最后，我们讨论了如何进一步发展这种有前途的方法来确定蛋白质和周围脂质的结构动力学的未来方向。
