The cannabinoid receptor subtype 2 (CB2), is a class-A membrane-bound G-protein coupled receptor (GPCR) and is currently an emerging research focus for treating neuroinflammation, pain, arthritis and various other associated disorders due to lack of CNS side effects relative to CB1. We prepared and validated homology models of the human CB2 receptor in its active state using a multi-template approach. Several homology models were built using multiple templates of known active state GPCRs, and the best model was used to dock CP 55, 940, a non-selective CB2 agonist. The best CP 55, 940-CB2 complex was embedded into a fully hydrated POPC lipid bilayer, equilibrated and then simulated for an extended MD simulation of 500 ns using the NAMD program. We observed and identified various conformational changes and key interactions of CP 55, 940 with the CB2 receptor, including the formation of extensive water-mediated hydrogen-bonded networks, aromatic π-π interactions and hydrophobic interactions. The insights gained from the present study could be useful for understanding the activation mechanism of CB2 receptor mediated by CB2 agonists.

Structural insights into conformation and dynamics of the cannabinoid CB2 receptor through an extended MD simulation of CP 55, 940–CB2 complex

253rd National Meeting (2017)

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