Universal Method for Embedding Proteins into Complex Lipid Bilayers for Molecular Dynamics Simulations

The growing interest toward membrane protein simulations calls for a universal and efficient protocol for embedding multiple proteins simultaneously into asymmetric many-component lipid membranes. To this end, here, we present a new and simple technique based on pushing proteins into a lipid membrane from its side by applying a high lateral pressure on the system. This approach is compatible with most (if not all) simulation software packages, and it is independent of external program codes. Most importantly, our protocol does not alter the lipid composition or the transmembrane lipid distribution of the host bilayer membrane. It can be employed with both atomistic and coarse-grained models, and it allows multiple proteins to be embedded into a membrane at the same time. It is shown that the protein structure is unaffected by the pressure applied to the system during the procedure, and the simulation resources required for protein insertion are shown to be modest, regarding both atomistic and coarse-grained simulation models.