Centre for Molecular Simulation and Department of Biological Sciences, University of Calgary, 2500 University Drive NW, Calgary, Alberta T2N 1N4, Canada.
J Phys Chem B. 2024 Jun 27;128(25):5987-5994. doi: 10.1021/acs.jpcb.4c01385. Epub 2024 Jun 11.
Membranes play essential roles in biological systems and are tremendously diverse in the topologies and chemical and elastic properties that define their functions. In many cases, a given membrane may display considerable heterogeneity, with localized clusters of lipids and proteins exhibiting distinct characteristics compared to adjoining regions. These lipid-protein assemblies can span nanometers to micrometers and are associated with cellular processes such as transport and signaling. While lipid-protein assemblages are dynamic, they can be stabilized by coupling between local membrane composition and shape. Due to the inherent difficulty in resolving atomistic details of membrane proteins in their native lipid environments, these complexes are notoriously challenging to study experimentally; however, molecular dynamics (MD) simulations might be a viable alternative. Here, we aim to assess the utility of coarse-grained (CG) MD simulations with the Martini force field for studying membrane curvature induced by transmembrane (TM) proteins that are reported to generate local curvature. The direction and magnitude of curvature induced by five different TM proteins, as well as certain lipid-protein and protein-protein interactions, were found to be in good agreement with available reference data.
膜在生物系统中起着至关重要的作用，其拓扑结构和化学及弹性特性在定义其功能方面具有极大的多样性。在许多情况下，给定的膜可能表现出相当大的异质性，局部脂质和蛋白质簇与相邻区域相比表现出不同的特征。这些脂-蛋白组装可以跨越纳米到微米的范围，并与细胞过程如运输和信号转导相关。虽然脂-蛋白组装是动态的，但它们可以通过局部膜组成和形状之间的耦合来稳定。由于在其天然脂质环境中解析膜蛋白原子细节的固有困难，这些复合物在实验上很难研究；然而，分子动力学（MD）模拟可能是一种可行的替代方法。在这里，我们旨在评估使用粗粒（CG）MD 模拟与 Martini 力场来研究跨膜（TM）蛋白引起的膜曲率的效用，这些蛋白据报道会产生局部曲率。发现五种不同的 TM 蛋白以及某些脂-蛋白和蛋白-蛋白相互作用引起的曲率的方向和幅度与可用的参考数据非常吻合。
