MemProtMD: Automated Insertion of Membrane Protein Structures into Explicit Lipid Membranes

Summary

There has been exponential growth in the number of membrane protein structures determined. Nevertheless, these structures are usually resolved in the absence of their lipid environment. Coarse-grained molecular dynamics (CGMD) simulations enable insertion of membrane proteins into explicit models of lipid bilayers. We have automated the CGMD methodology, enabling membrane protein structures to be identified upon their release into the PDB and embedded into a membrane. The simulations are analyzed for protein-lipid interactions, identifying lipid binding sites, and revealing local bilayer deformations plus molecular access pathways within the membrane. The coarse-grained models of membrane protein/bilayer complexes are transformed to atomistic resolution for further analysis and simulation. Using this automated simulation pipeline, we have analyzed a number of recently determined membrane protein structures to predict their locations within a membrane, their lipid/protein interactions, and the functional implications of an enhanced understanding of the local membrane environment of each protein.

Graphical Abstract

Highlights

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  A simulation pipeline for predicting the location of a membrane protein in a bilayer

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  A protocol for identifying novel membrane protein structures in the PDB

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  Analysis of lipid binding sites and local bilayer deformation by membrane proteins

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  Functional implications from enhanced understanding of local membrane environments

Abstract

Stansfeld et al. present MemProtMD, an automated pipeline for molecular simulations to insert membrane protein structures into explicit lipid bilayer membranes. An analysis of simulations of all known membrane protein structures reveals details of protein-induced membrane deformation and rules for residue distribution, and facilitates refinement of membrane proteins.