Dissimilar interaction of CB1/CB2 with lipid bilayers as revealed by molecular dynamics simulation

Cannabinoid receptors CB1 and CB2 are a striking class of transmembrane proteins involved in a high number of important biological processes. In spite of the inherent similarity (40% in aminoacid sequence) these receptors are found in different cell environments. In addition to this, CB1 activity has been intimately associated with lipid rafts whereas CB2 has not. In this work we have performed a 50 nanosecond molecular dynamics simulation of the inactive conformations of both receptors inserted in a POPC lipid bilayer. Although in both cases the overall protein structure is maintained along the entire simulation we have found important differences in the protein-lipid interaction. While CB1 tends to distort the lipid bilayer regularity, especially in the extracellular moiety, CB2 has a minor influence on the lipid distribution along the plane of the bilayer. This observation is consistent with some experimental facts observed in these cannabinoid receptors with regard to lipid/protein interaction. © the Owner Societies 2011.Thanks are due to the MICINN (MAT2009-12364 and CTQ2009-07664 projects) for financial support. The authors are also grateful to the ‘‘Centro de Supercomputacio´n de Galicia’’ (CESGA) and the ‘‘Centro de Supercomputacio´n y Visualizacio´n de Madrid’’ (CESVIMA) for allocation of CPU time on the FINISTERRAE and MAGERIT supercomputers, respectively. The authors also acknowledge ‘‘SGAI-CSIC’’ for technical support during the simulationsPeer Reviewe