Modelagem molecular de processos de agregação do peptídeo β-amilóide aβ(1-42) e sua desativação com complexos de Pt(II)

Abstract

In the present work, theoretical methods were used to analyze the structural, thermodynamic and kinetic properties of β-amyloid peptide aggregates and its adducts formed with phenanthroline derivatives platinum(II) complex, which are considered potentials regulators of Alzheimer’s disease. Through molecular modeling techniques, we propose a model of structure/reactivity/stability to this class of metal compounds with hitidine (His) residues. Using Molecular Dynamic (MD) simulations was possible to propose the agglomerative profile among the peptides in which His residues of were mapped in a topological and identified as the responsible for the clusters’s stability. The obtained results are in agreement with the experimental evidences, which suggests that blocking the His sites, favors the decrease of formation of the Aβ(1-42) agglomerates. In the second part of the work, the reaction kinetics between Pt(II) complexes with Aβ(1-42) was investigated using quantum methods (QM) and hybrid (QM/MM). The biological target was divided into 3 parts containing 1, 10 and 42 amino acids residues (AA) respectively, so that it was possible to note the deagglomerative response induced by this class of metal compounds in the formed adducts, being feasible the development of possible new drugs against Alzheimer disease.