Encoding mu-opioid receptor biased agonism with interaction fingerprints

Exploring biased activation characteristics by molecular dynamics simulation and machine learning for the μ-opioid receptor

“…66 Furthermore, mutation studies conducted on δOR have demonstrated that mutations like N3.35A and N3.35V can induce constitutive β-arrestin activity in the receptor. 70 The molecular docking and simulation study also confirmed that N3.35 is a key residue for μOR interaction with biased ligands. 70 Therefore, we speculate that the hydrogen bonding between these residues and endomorphin2 would enhance β-arrestin-biased signaling.…”

“…70 The molecular docking and simulation study also confirmed that N3.35 is a key residue for μOR interaction with biased ligands. 70 Therefore, we speculate that the hydrogen bonding between these residues and endomorphin2 would enhance β-arrestin-biased signaling.…”

“…86 Bruno et al revealed the involvement of L2.57 and Y2.64 in the biased activation, derived from μOR bound by unbiased ligands and G protein-biased ligands. 70 I234 5.40 in the middle of TM5 is presented in the top 20 important residues, indicating its important role in distinguishing the conformations induced by the two different biased agonists of μOR. This observation is in line with the findings of Ambrose et al , which emphasize the significance of residue 5.40 on TM5 in the D2R ligand-specific conformational state, including partial agonists, full agonists, and inverse agonists.…”