Molecular Dynamics Simulations of Membrane Proteins: Building Starting Structures and Example Applications

Abstract

Located at the interface between the cell and organelle interior and exterior, membrane proteins are key players in a number of fundamental biological processes. In recent years, molecular dynamics simulations have become an increasingly important tool in the study of membrane proteins. Increases in computer power and the ongoing development in atomistic and coarse-grained MD techniques now permit simulations of membrane protein systems on a size and time scale that would have been impossible only a few years ago. At the beginning of each membrane protein simulation stands the generation of a suitable starting structure which can be done by either constructing the bilayer around the protein or by inserting the protein into a pre-equilibrated membrane patch. Here we review the current state of the art of the available techniques and carry out application benchmarks using five example membrane proteins of different size and transmembrane structure. We conclude this paper reviewing recent examples of molecular dynamics studies representing three major classes of membrane proteins: G protein-coupled receptors, channels and transporters. Keywords: Membrane protein, Molecular dynamics simulation, Protein insertion, Lipid bilayer, Hydrophobic belt, homology modeling, bilayer-embedded membrane protein, coarse-grained, Gram-negative bacteria, MARTINI force field, transmembrane protein