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
محورهای موضوعی : Organic and Inorganic synthesis
Diba Aslani Firozabadi
1
(
Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad, Iran
)
Mohammad Reza Bozorgmehr
2
(
Dept. of Chemistry, Faculty of ScienceMashhad branch, Islamic Azad University, Mashhad, Iran
)
S. Ali Beyramabadi
3
(
Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad, Iran
)
Sharareh Mohseni
4
(
Department of Chemistry, Quchan Branch, Islamic Azad University, Quchan, Iran
)
کلید واژه: Alzheimer, metal, reactivity, beta amyloid, aggregation,
چکیده مقاله :
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.
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.
[1] Rogers, J., Cooper, N.R., Webster, S., Schultz, J., McGeer, P.L., Styren, S.D., Civin, W.H., Brachova, L., Bradt, B. and Ward, P. (1992) Proceedings of the National Academy of Sciences, 89, 10016.
[2] Mantyh, P.W., Ghilardi, J.R., Rogers, S., DeMaster, E., Allen, C.J., Stimson, E.R. and Maggio, J.E. (1993) Journal of neurochemistry, 61, 1171.
[3] Firozabadi, D.A., Bozorgmehr, M.R., Beyramabadi, S.A. and Mohseni, S. (2023) Current Proteomics, 20, 145.
[4] Bush, A.I., Pettingell Jr, W.H., Paradis, M. and Tanzi, R.E. (1994) Journal of Biological Chemistry, 269, 12152.
[5] Crescenzi, O., Tomaselli, S., Guerrini, R., Salvadori, S., D'Ursi, A.M., Temussi, P.A. and Picone, D. (2002) European journal of biochemistry, 269, 5642.
[6] Turner, M., Mutter, S.T. and Platts, J.A. (2019) Journal of Biomolecular Structure and Dynamics, 37, 4590.
[7] DeLano, W.L. (2004) Delano Scientific: San Carlos, CA, USA, 1.
[8] Zielkiewicz, J. (2005) The Journal of chemical physics, 123.
[9] Lemak, A. and Balabaev, N. (1994) Molecular Simulation, 13, 177.
[10] Hess, B., Bekker, H., Berendsen, H.J. and Fraaije, J.G. (1997) Journal of computational chemistry, 18, 1463.
[11] Miyamoto, S. and Kollman, P.A. (1992) Journal of computational chemistry, 13, 952.
[12] Berendsen, H.J., van der Spoel, D. and van Drunen, R. (1995) Computer physics communications, 91, 43.
[13] Housaindokht, M.R., Bozorgmehr, M.R. and Bahrololoom, M. (2008) Journal of theoretical biology, 254, 294.
[14] Sohrabi, M., Bozorgmehr, M.R. and Momen-Heravi, M. (2024) Journal of Biomolecular Structure and Dynamics, 1.
[15] BORGHESANI, V., ALIES, B., SAYEN, S., GUILLON, E., FALLER, P. and HUREAU, C. (2016) Casa Convalescència ALBA Synchrotron 7-10 June 2016 Barcelona, 89.
[16] Hureau, C. (2012) Coordination Chemistry Reviews, 256, 2164.
[17] Pietrucci, F. (2017) Reviews in Physics, 2, 32.
