The effect of fulvic acid on pre- and postaggregation state of Aβ17-42: Molecular dynamics simulation studies

Abstract

Alzheimer's disease (AD), a neurodegenerative disorder, is directly related to the aggregation of Aβ peptides. These peptides can self-assemble from monomers to higher oligomeric or fibrillar structures in a highly ordered and efficient manner. This self-assembly process is accompanied by a structural transition of the aggregated proteins from their normal fold into a predominantly β-sheet secondary structure. 14 ns molecular dynamics simulation revealed that fulvic acid interrupted the dimer formation of Aβ17-42 peptide while in its absence Aβ17-42 dimer formation occurred at ∼ 12 ns. Additionally, fulvic acid disrupted the preformed Aβ17-42 trimer in a very short time interval (12 ns). These results may provide an insight in the drug design against Aβ17-42 peptide aggregation using fulvic acid as lead molecule against Aβ17-42 mediated cytotoxicity and neurodegeneration. © 2012 Elsevier B.V. All rights reserved.