Ligand discrimination during virtual screening of the CB1 cannabinoid receptor crystal structures following cross-docking and microsecond molecular dynamics simulations.

ABSTRACT: The therapeutic potential of the CB1 cannabinoid receptor remains underexploited with only a few synthetic ligands on the market. The crystal structures of both the inactive and active-state CB1 receptor have recently been solved, allowing for unprecedented opportunities in structure-based drug discovery applications such as virtual screening. In this study, we have investigated the virtual screening performance of the active and inactive-state CB1 crystal structures and their ability to discriminate between agonist and inverse agonist/antagonist ligands. The ligands of inactive and active-state CB1 receptor crystal structures were then swapped via cross-docking and the resulting structures were subjected to microsecond molecular dynamics (MD) simulations, followed by virtual screen

SUBMITTER: Loo JSE 

PROVIDER: S-EPMC9064321 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature