Centre for Molecular Simulation and Department of Biological Sciences , University of Calgary , 2500 University Drive NW , Calgary , Alberta T2N 1N4 , Canada.
Groningen Biomolecular Sciences and Biotechnology Institute and Zernike Institute for Advanced Materials , University of Groningen , Nijenborgh 7 , 9747 AG Groningen , The Netherlands.
Chem Rev. 2019 May 8;119(9):5775-5848. doi: 10.1021/acs.chemrev.8b00451. Epub 2019 Feb 13.
Membrane lipids interact with proteins in a variety of ways, ranging from providing a stable membrane environment for proteins to being embedded in to detailed roles in complicated and well-regulated protein functions. Experimental and computational advances are converging in a rapidly expanding research area of lipid-protein interactions. Experimentally, the database of high-resolution membrane protein structures is growing, as are capabilities to identify the complex lipid composition of different membranes, to probe the challenging time and length scales of lipid-protein interactions, and to link lipid-protein interactions to protein function in a variety of proteins. Computationally, more accurate membrane models and more powerful computers now enable a detailed look at lipid-protein interactions and increasing overlap with experimental observations for validation and joint interpretation of simulation and experiment. Here we review papers that use computational approaches to study detailed lipid-protein interactions, together with brief experimental and physiological contexts, aiming at comprehensive coverage of simulation papers in the last five years. Overall, a complex picture of lipid-protein interactions emerges, through a range of mechanisms including modulation of the physical properties of the lipid environment, detailed chemical interactions between lipids and proteins, and key functional roles of very specific lipids binding to well-defined binding sites on proteins. Computationally, despite important limitations, molecular dynamics simulations with current computer power and theoretical models are now in an excellent position to answer detailed questions about lipid-protein interactions.
膜脂以多种方式与蛋白质相互作用，从为蛋白质提供稳定的膜环境到在复杂且受到良好调节的蛋白质功能中发挥详细作用。实验和计算方面的进展正在脂质-蛋白质相互作用这一快速发展的研究领域中汇聚。在实验方面，高分辨率膜蛋白结构的数据库不断扩大，同时也具备了识别不同膜中复杂脂质组成、探测脂质-蛋白质相互作用具有挑战性的时间和长度尺度、以及将脂质-蛋白质相互作用与各种蛋白质的功能联系起来的能力。在计算方面，更精确的膜模型和更强大的计算机现在能够详细研究脂质-蛋白质相互作用，并与实验观察结果进行重叠，以验证和联合解释模拟和实验。在这里，我们综述了使用计算方法研究详细的脂质-蛋白质相互作用的论文，并简要介绍了实验和生理背景，旨在全面涵盖过去五年中模拟论文。总的来说，通过一系列机制，包括调节脂质环境的物理性质、脂质和蛋白质之间的详细化学相互作用以及非常特定的脂质与蛋白质上特定结合位点的关键功能作用，出现了一幅复杂的脂质-蛋白质相互作用图景。在计算方面，尽管存在重要限制，但目前的计算机能力和理论模型的分子动力学模拟现在处于回答有关脂质-蛋白质相互作用的详细问题的极佳位置。
