Interactions with lipids are important in the function of membrane proteins  and in the organization of cell membranes. Molecular dynamics simulations allow us to explore structural, energetic, and dynamic aspects of these interactions. Coarse-grained (CG) simulations in mixed lipid bilayers allow identification of lipid interaction sites, which may be probed further by estimation of free energy landscapes to explore lipid specificity, and by atomistic simulations to refine models of the structure and dynamics of lipid binding. This approach has been applied to a number of membrane proteins, including transporters, ion channels, and receptors. Simulations of lipid interactions with Class A GPCRs has revealed binding sites for cholesterol and PIP2, subsequently confirmed by both MS  and structural data. Interactions with PIP2 have been shown to be dependent on the activation state of the receptor, suggesting a functional role for the lipid via allosteric modulation . Interactions of lipids with other classes of GPCRs have been explored, including of cholesterol and PIP2 with the Class F GPCR Smoothened . Our analysis of the interactions of lipids with ion channels have also focussed on cholesterol and PIP2, both of which are allosteric modulator of a number of ion channel families. PIP2 interactions have been characterised for Kir channels, and more recently for members of the TRP channel family . Simulations of large membrane systems containing multiple copies of Kir channels suggest that the lipid composition of the bilayer can modulate channel-channel interactions within crowded membranes.
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