Park Sang-Jun, Schnitzer Kyle A, Kovalenko Alexey, Cherepanov Stanislav, Patro L Ponoop Prasad, Song Zigang, Pogozheva Irina D, Lomize Andrei L, Im Wonpil
Department of Computer Science and Engineering, Lehigh University, 111 Research Drive, Bethlehem, PA 18015, United States.
Department of Electrical Engineering and Computer Science, College of Engineering, University of Michigan, 1221 Beal Ave, Ann Arbor, MI 48109-2102, United States.
J Mol Biol. 2025 Aug 1;437(15):168966. doi: 10.1016/j.jmb.2025.168966. Epub 2025 Jan 27.
Molecular dynamics (MD) simulations in explicit lipid bilayers enable modeling of protein-lipid interactions essential for membrane protein functions and regulation. The newly developed computational web tool, OPRLM (Orientations of Proteins in Realistic Lipid Membranes), automates the assembly of membrane protein structures with explicit lipids corresponding to 18 biological membrane types with symmetric or asymmetric lipid distributions, as well as 5 types of two-component lipid bilayers with varying cholesterol content. Built upon the CHARMM-GUI toolset and the PPM method, OPRLM simplifies the setup of complex simulation system involving integral and/or peripheral membrane proteins with explicit lipid mixtures and generates all necessary files for subsequent all-atom MD simulations. OPRLM has successfully generated protein-membrane systems for 286 tested protein structures in various biomembranes, including 138 structures containing ligands. The OPRLM database, an advanced successor of the OPM database, includes explicit protein-lipid systems for tested proteins in their native biomembranes. It provides coordinates of integral and peripheral membrane proteins from the Protein Data Bank embedded in planar or curved implicit lipid bilayers. Additionally, it includes the classification of proteins into types, superfamilies, and families, along with the information on intracellular localizations and membrane topology and visualization options. The OPRLM web tool and the database are publicly accessible at https://oprlm.org.
在明确的脂质双分子层中进行分子动力学（MD）模拟，能够对膜蛋白功能和调节所必需的蛋白质 - 脂质相互作用进行建模。新开发的计算网络工具OPRLM（真实脂质膜中蛋白质的方向）可自动组装膜蛋白结构，这些结构带有对应18种具有对称或不对称脂质分布的生物膜类型的明确脂质，以及5种具有不同胆固醇含量的双组分脂质双分子层。基于CHARMM - GUI工具集和PPM方法构建，OPRLM简化了涉及带有明确脂质混合物的整合和/或外周膜蛋白的复杂模拟系统的设置，并生成用于后续全原子MD模拟的所有必要文件。OPRLM已成功为各种生物膜中的286个测试蛋白结构生成了蛋白质 - 膜系统，其中包括138个含有配体的结构。OPRLM数据库是OPM数据库的高级继任者，包括测试蛋白在其天然生物膜中的明确蛋白质 - 脂质系统。它提供了嵌入平面或弯曲隐式脂质双分子层中的来自蛋白质数据库的整合和外周膜蛋白的坐标。此外，它还包括蛋白质按类型、超家族和家族的分类，以及关于细胞内定位、膜拓扑结构和可视化选项的信息。OPRLM网络工具和数据库可在https://oprlm.org上公开访问。
