Fig. 7.

a Detailed binding mode of lemborexant in complex with OX2R (receptor: light orange, ligand: cyan, PDB: 7XRR), where steric hindrance of T135^3.33 only allows one orientation of the ligand. b Detailed binding mode of lemborexant in complex with OX1R (receptor: light pink, ligand: yellow, PDB: 6TOT), where small side chain of A127^3.33 accounts for two orientations of the ligand. c Abridged general view of employing MD simulation to predict the conformation of the ligand before receptor binding, to improve K_on values. d 2D structure of lemborexant is shown for clarity