|rings a bell, may have already put this up and now it's back as eCollection.....|
PLoS One. 2019 Jul 23;14(7):e0220025. doi: 10.1371/journal.pone.0220025. eCollection 2019.
Cannabidiol binding and negative allosteric modulation at the cannabinoid type 1 receptor in the presence of delta-9-tetrahydrocannabinol: An In Silico study.
Chung H1, Fierro A2, Pessoa-Mahana CD1.
Pharmacy Department, Faculty of Chemistry, Pontificia Universidad Católica de Chile, Santiago, Chile.
Organic Chemistry Department, Faculty of Chemistry, Pontificia Universidad Católica de Chile, Santiago, Chile.
Recent evidence has raised in discussion the possibility that cannabidiol can act as a negative allosteric modulator of the cannabinoid type 1 receptor. Here we have used computational methods to study the modulation exerted by cannabidiol on the effects of delta-9-tetrahydrocannabinol in the cannabinoid receptor type 1 and the possibility of direct receptor blockade. We propose a putative allosteric binding site that is located in the N-terminal region of receptor, partially overlapping the orthosteric binding site. Molecular dynamics simulations reveled a coordinated movement involving the outward rotation of helixes 1 and 2 and subsequent expansion of the orthosteric binding site upon cannabidiol binding. Finally, changes in the cytoplasmic region and high helix 8 mobility were related to impaired receptor internalization. Together, these results offer a possible explanation to how cannabidiol can directly modulate effects of delta-9-tetrahydrocannabinol on the cannabinoid receptor type 1.