Background: Aβ (amyloid-beta peptide) is a key molecule in the development of Alzheimer's disease, forming toxic aggregates in the brain. The use of metal-based compounds, particularly Pt(II) complexes, to prevent Aβ aggregation is one of the therapeutic strategies for Alzheimer's.
Aim: Modelling the interactions of Pt(II) complexes with various fragments of Aβ using computational quantum mechanics and molecular mechanics methods with the hope of finding a curing way to treat Alzheimer's desease.
Methodology: The interactions of several compounds effective in Alzheimer's treatment with Aβ were investigated through docking calculations using AutoDock software. Curcumin was selected as a ligand for complex formation with platinum based on its binding free energy (∆G), inhibition constant, and anti-Alzheimer properties. Four of the reported effective platinum complexes for Alzheimer's treatment, along with PtCl(cur)(DMSO), were examined using docking calculations to identify the most suitable complex for interaction with Aβ (the highest interaction level). The complex PtCl(cur)(DMSO) was chosen for molecular dynamics calculations and MD simulations due to its greater stability, lower inhibition constant, and more negative binding free energy. Three compounds PtCl(cur)(DMSO), curcumin (Cur), and rosmarinic acid (RA) were calculated using quantum mechanical methods (DFT method) to investigate the extent of π-stacking interactions with the aromatic rings of three amino acids: His, Tyr, and Phe in the structure of amyloid beta peptide. Molecular dynamical calculations were performed using the AMBER99SB-ILDN force field for simulation of two systems, monomeric Aβ as a control and monomeric Aβ with the PtCl(cur)(DMSO) complex using GROMACS software. This simulation aimed to investigate the inhibitory effect of the platinum curcumin complex on Aβ aggregation. Findings: In this study, quantum mechanical calculations indicated that the π-stacking interaction energy (ΔEint) of P