Abstract Recent insight has implicated the formation of β-amyloid fibril formation as a culpable process for the progression of Alzheimer's disease. Amyloid-β (Aβ) is a peptide naturally secreted by neurons in a random coil structure. It has been deduced that a conformational transition from a random coil to a β-pleated sheet is responsible for Aβ's neurotoxicity. The disruption of a His-Asp salt bridge has been found to inhibit this conformational change to the β-pleated sheet—a phenomenon observed in vitro when the peptides are incubated with melatonin. To further investigate this interaction between melatonin and histidine, the binding was investigated at the B3LYP/6-31g(d) level of theory for the two lowest energy conformers of melatonin: χ 2 = g +, χ 3 = anti , χ 4 = g +, and χ 2 = g −, χ 3 = anti , χ 4 = g −, and imidazolium. The most favorable interaction was found to be an intersecting one; the respective counterpoise corrected binding energies were found to be −17.8 and −19.8 kcal/mol.