The binding of kojic acid dimer and its Zn(II) and Cu(II) complexes at the beta-amyloid peptide: A DFT-based computational assessment

The increasing number of people afflicted by Alzheimer's disease in the world requires a constant intensification of the efforts to seek for new agents capable of dismantling the molecular mechanisms underlying the onset and development of this neurodegenerative disorder. In this study, the binding of kojic acid dimer (KAD), and its adducts with Zn(II) and Cu(II) to the beta-amyloid peptide (Aβ) have been investigated by means of density functional theory-based computational approaches. We envisioned that the capability of KAD to inhibit the amyloid cascade may be exerted in concomitance and/or supported by the coordination of either Zn(II) or Cu(II). Thus, the structure and binding features of KAD-Zn and KAD-Cu metal complexes were computationally assessed to gain an atomistic insight of the possible Aβ inhibition. Our calculations evidenced that Zn(II), but not Cu(II), might act in concert with KAD in the binding of the Aβ peptide. Furthermore, we identified the Aβ_13–20 region as a plausible binding site for KAD and KAD-Zn complexes, emphasizing its relevance for future experimental studies.