Open AccessPrediction of essential binding domains for the endocannabinoid N-arachidonoylethanolamine (AEA) in the brain cannabinoid CB1 receptor
Author(s) -
JoongYoun Shim
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0229879
Subject(s) - cannabinoid receptor , endocannabinoid system , cannabinoid , receptor , docking (animal) , chemistry , binding site , tetrahydrocannabinol , biochemistry , antagonist , medicine , nursing
Δ 9 -tetrahydrocannabinol (Δ 9 -THC), the main active ingredient of Cannabis sativa (marijuana), interacts with the human brain cannabinoid (CB1) receptor and mimics pharmacological effects of endocannabinoids (eCBs) like N -arachidonylethanolamide (AEA). Due to its flexible nature of AEA structure with more than 15 rotatable bonds, establishing its binding mode to the CB1 receptor is elusive. The aim of the present study was to explore possible binding conformations of AEA within the binding pocket of the CB1 receptor confirmed in the recently available X-ray crystal structures of the CB1 receptor and predict essential AEA binding domains. We performed long time molecular dynamics (MD) simulations of plausible AEA docking poses until its receptor binding interactions became optimally established. Our simulation results revealed that AEA favors to bind to the hydrophobic channel (HC) of the CB1 receptor, suggesting that HC holds essential significance in AEA binding to the CB1 receptor. Our results also suggest that the Helix 2 (H2)/H3 region of the CB1 receptor is an AEA binding subsite privileged over the H7 region.