The effect of fulvic acid on pre- and postaggregation state of Aβ(17-42): molecular dynamics simulation studies.

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. 14ns molecular dynamics simulation revealed that fulvic acid interrupted the dimer formation of Aβ(17-42) peptide while in its absence Aβ(17-42) dimer formation occurred at ~12ns. Additionally, fulvic acid disrupted the preformed Aβ(17-42) trimer in a very short time interval (12ns). These results may provide an insight in the drug design against Aβ(17-42) peptide aggregation using fulvic acid as lead molecule against Aβ(17-42) mediated cytotoxicity and neurodegeneration.