Lipid Protein Interactions Of G Protein Coupled Receptors

G Protein - Coupled Receptors (GPCRs) are a large family of membrane proteins involved in a large array of biochemical processes. Recent studies show that in order to explain the activity of GPCRs, their lipid environment has to be taken into account. Most notably, the interaction of GPCRs with cholesterol molecules has been the center of focus of several studies conducted in the past few years. To understand this lipid-protein dynamics, we have carried out large-scale molecular dynamics simulations, using the MARTINI coarse-grained model, of several biologically important GPCRs (e.g. the human chemokine (CXCR1) receptor involved in breast cancer, and the delta opioid receptor important in pain sensing). Our simulation setup consists of four copies of proteins embedded in a 40nm x 40nm complex lipid bilayer, composed of more than 60 lipid types and simulated for 30 microseconds. Here, we present our results on the lipid organization at different distances from each protein copy, and show their relative lipid enrichment. In addition, we present our results on the lipid distribution and the interactions of cholesterol with GPCRs. We believe that the simulation setup design we have employed and the long time scales we have achieved offer a unique perspective on the lipid-protein interaction dynamics of GPCRs.