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.
1
Pharmacy Department, Faculty of Chemistry, Pontificia Universidad Católica de Chile, Santiago, Chile.
2
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. |
