Amyloid-�, an intrinsically disordered protein is the major molecular player in Alzheimer's disease (AD). Recent studies on neuronal cells and mouse models have shown that small soluble aggregates of this peptide have a stronger correlation with disease cytotoxicity than the insoluble fibrillar aggregates. We are interested in one such toxic species of Amyloid-beta- a dodecamer called the �Globulomer�. Low solution concentrations and partial homogeneity of the �Globulomer� makes structural characterization of the species difficult, which is very crucial for designing therapeutic molecules. We are looking into the possibility that the toxic species might constitute an ensemble of structures with different quaternary or tertiary conformations. Using molecular dynamics simulations, we aim to compare the ensemble-averaged NMR observables and amide protection factors with the available experimental data for validation of our structural hypothesis.

Molecular dynamics simulations of soluble toxic oligomers of Amyloid-�

248th National Meeting (2014)

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