Cmem Builder: An Automated Tool for Curved Membrane Construction in Molecular Dynamics Simulations.

Abstract

Membrane curvature is a fundamental property of biological membranes, driving essential processes such as endocytosis, vesicle formation, and mechanotransduction. Molecular dynamics (MD) simulations have become a powerful approach for studying curved membrane systems, providing atomistic insights into curvature-driven phenomena and protein-membrane interactions. However, online platforms like CHARMM-GUI and CGMD focus on constructing flat bilayers or vesicles and lack support for generating curved membranes with defined geometries. Local tools, while more flexible, often do not incorporate protein-specific curvature features, such as those from the Orientations of Proteins in Membranes (OPM) database, which are critical for accurately modeling protein-lipid interactions in curved environments. To address these limitations, we developed Cmem Builder, a novel and user-friendly web server for automating the generation of curved lipid membranes and membrane-protein complexes for coarse-grained (CG) MD simulations using the MARTINI force field. Cmem Builder specializes in generating Z-axis symmetric curved membrane shapes, supports curvature profiles derived from OPM database or custom geometries, allows extensive control over lipid composition, and ensures lipid placement through geometric sampling. The tool has been successfully applied to classical curved membrane systems, including Piezo1 and BAR proteins, as well as plasma membranes with asymmetric lipid compositions, demonstrating its accuracy and efficiency. In total, Cmem Builder provides a robust and accessible platform for exploring the complex dynamics of curved membrane systems. The tool is freely available at https://cmembuilder.com.