Sequence alignment used in homology modeling. Target sequence: OX1R [UniProt:O43613]. Template sequences: OX2R [PDB:4S0V], NTSR1 [PDB:4GRV] and CXCR4 [PDB:3ODU]. Orange: orexin receptor residues found to be important by site-directed mutagenesis. Cyan: NTSR1 residues that interact with neurotensin8-13. Boxed: OX2R residues within 4 Å of suvorexant. Italics: helix 8 from dopamine D3 receptor [PDB:3PBL]. Cylinders and arrows: TM helices and β strands seen in template structures. Numbering refers to OX1R. Triangle: x.50 residue. *: TM3–ECL2 disulfide bridge. Gray: identical residues between OX1R and templates. Illustrated with Alscript .