Figure 5.

Electron density in the MT₁ ligand-binding pocket. (a) Ligand electron density for MT₁ (white cartoon) after ligand exchange of agomelatine (Ago) to 2-phenylmelatonin (2-PMT; orange). (b) Ligand electron density after incorrect placement of the transient ligand Ago (cyan) and refinement starting from the same molecular-replacement structure (see Section 2). Both structural models are of comparable stereochemical quality, but the structure refined with Ago shows slightly worse refinement statistics (R and R _free of 0.257 and 0.314 compared with 0.257 and 0.308, respectively). 2mF _o − DF _c maps (blue mesh) are contoured at 1σ. mF _o − DF _c electron-density difference maps contoured at ±3.5σ (green and red for positive and negative peaks, respectively) show strong (∼6.7σ) positive difference density for the missing phenyl ring in the structure refined with Ago.