Computational insights into the subtype selectivity and "message-address-efficacy" mechanisms of opioid receptors through JDTic binding and unbinding.

ABSTRACT: In drug design and discovery, binding affinity and selectivity are two basic properties of a drug candidate. Opioid receptors (ORs) are the main targets of strong analgesics. Like some other class A members of G-protein-coupled receptors (GPCRs), ORs exhibit complex selectivity on their ligands. The diversity of binding activity and selectivity among opioids has deeply attracted researchers for a long time. To investigate the subtype selectivity of μ, δ and κ ORs in detail, using the κ-selective antagonist JDTic as a probe, we performed a series of computational simulations, including molecular dynamics and metadynamics, on JDTic-μ/δ/κ-OR complexes. From the simulations, we found that the decisive factor of JDTic selectivity on the μ-subtype was the 2.63 position, which affected the effica

SUBMITTER: Cheng JX 

PROVIDER: S-EPMC5843831 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature