Comparative Analysis of Histidine-14 Reactivity in C-terminal truncated beta-amyloid peptide in the Presence of Copper and Zinc Ions: Insights from Molecular Dynamics Simulations and Density Functional Theory

Subject Areas :

Diba Aslani Firozabadi ¹ , Mohammad Reza Bozorgmehr ² , S. Ali Beyramabadi ³ , Sharareh Mohseni ⁴

1 - Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad, Iran
2 - Dept. of Chemistry, Faculty of ScienceMashhad branch, Islamic Azad University, Mashhad, Iran
3 - Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad, Iran
4 - Department of Chemistry, Quchan Branch, Islamic Azad University, Quchan, Iran

Received: 2024-07-19 Accepted : 2024-09-11 Published : 2024-09-20

Keywords: Alzheimer, metal, reactivity, beta amyloid, aggregation,

Abstract :

This study investigates the reactivity of the beta-amyloid peptide, particularly focusing on its interactions with copper and zinc ions, which are relevant to the progression of Alzheimer's disease. Molecular dynamics simulations were performed to explore the effects of copper and zinc ions on the stability and binding affinity of the peptide. The presence of copper ions was found to decrease the relative stability of peptide. Conformational analysis revealed that copper ions preferentially bind to the N-terminal residues, with a particularly high affinity for His14. The addition of zinc ions reduced the overall binding affinity of copper ions to the peptide but did not significantly alter the strong interaction with His14. Density functional theory (DFT) calculations on the sampled peptide structures provided quantum descriptors, including the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies, which are indicative of reactivity. The results suggest a significant decrease in the reactivity of His14 in the presence of copper ions, with a further reduction observed in the combined presence of both copper and zinc ions. These findings contribute to understanding the molecular mechanisms underlying metal ion-induced conformational changes in beta-amyloid peptides and their role in Alzheimer's disease.

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