Comparison of the effect of membrane lipids on the µ opioid receptor by studying crystallographic, all-atoms and coarse-grained models

Opioid receptors, whose structures were revealed in 2012, are part of G-protein coupled receptors (GPCRs), the target of 50 % of drugs on the actual market [1]. The structural and functional properties of these transmembrane proteins are clearly affected by the lipid environment [2].
To understand these processes, classical molecular dynamics (MD) simulations can provide numerous clarifications. In this work, we present modeling studies of a coarse-grained (CG) and all-atoms (AA) patch of membrane with POPC (1-palmitoyl-2-oleyl-sn-glycero-3-phosphocholine) by molecular dynamics (DM) for 1 μs, and the crystallized structure of the μ receptor with a morphinan antagonist [1]. Particularly, we compare the effect of lipids with the tilt angle of the protein and its helices and the distance between lipids and amino acids for these three models.
We further will use other lipids such as cholesterol to characterize the different bindings of the lipids versus μ OR and show potential new conformatins of μ OR.

References:
[1] Manglik A. et al. (2012) Nature 485: 321-327
[2] Prasanna X. et al. (2014) Biophysical Journal 106: 1290-1300