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: χ2=g+, χ3=anti, χ4=g+, and χ2=g-, χ3=anti, χ4=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 -19.8kcal/mol.
- Amyloid beta peptide
- Density functional theory
- Neurofibrillary tangles
ASJC Scopus subject areas
- Physical and Theoretical Chemistry
- Computational Theory and Mathematics
- Atomic and Molecular Physics, and Optics