Membrane lipid composition: an important but neglected aspect of membrane protein simulation

Membranes are heterogeneous 2D mixtures of integral membrane proteins and lipids. The lipid environment and individual lipid molecules are increasingly being shown to affect the structure, dynamics, and function of membrane proteins. Computational methods and power have advanced to the point where it is feasible to simulate membrane proteins in simplified biologically realistic lipid mixtures, although lipidomic data remains a limitation. However, as we illustrate for computational studies of the mu opioid receptor, simple one- or two-component lipid bilayers remain the most common type of 'model membrane' used in molecular dynamics simulation of membrane proteins. We argue that this is no longer acceptable and provide some guidance on selecting a biologically relevant lipid composition.