Memprotmd: Restoring Membrane Protein Structures to their Bilayer Environments

Abstract

Membrane protein structural biology is one of the key biochemical challenges of the coming decade. With continuous improvements to the experimental methods used there is a predicted exponential growth in the number of high-resolution membrane proteins structures. Nevertheless, these biological assemblies are usually resolved in the absence of the native lipid environment. Coarse-Grained molecular dynamics (CGMD) simulations provide a means for assessing the assembly and interactions of molecular complexes at a reduced level of representation. This method has been shown to be accurate in predicting the insertion position of proteins within a cell membrane, with many membrane proteins immersed in their native environment and deposited in our database of CGMD membrane protein simulations (CGDB). We have now automated the procedure, so that new membrane protein structures are automatically detected and inserted into a lipid bilayer upon their release in the Protein Data Bank (PDB). The resultant simulations are then assessed for protein-lipid interactions, bilayer deformation, lipid diffusion, protein tilt and pore access pathways. The lipid composition within the assembled complexes are then transformed to better reflect the membrane environment of the native protein and also converted to an atomistic resolution to investigate the dynamics in full atomic detail. We have applied this methodology to a number of recently resolved membrane protein structures to assess their location within the membrane, structural stability and to identify specific lipid binding sites.