The human Amyloid Precursor Protein (APP) is vital to the development of Alzheimer's isease. The beta peptides of APP, in particular Aβ42, accumulate into intercellular plaques in the brain that inhibit neuron function. It is hypothesized this may result from a misregulation in the transportation of APP. As such, it is important to understand the behavior of the binding region of APP. In this project, we obtained the membrane-spanning APP C99 NMR structure (C-terminal 99 residues of APP) from the Sanders' laboratory at Vanderbilt University. We then truncated the structure to the last 42 residues, which has been shown to exhibit binding behavior with related transport proteins. Utilizing the Amber software package, we ran two 3.5 microsecond unrestrained molecular dynamics simulations on the TIP3P-solvated and neutralized Aβ42 molecule. We used RMSD as well as secondary and tertiary structure analyses to evaluate the simulations and produce starting conformations for further studies. The occurrence of a C-terminal alpha helix was consistent throughout both simulations, a motif that could have significant implications in  future research. Several other helices were observed throughout the simulations across the peptide. With these results we are able to fully characterize the secondary structures and some tertiary structures in the human APP-C42 peptide.

Characterizing the folding of the amyloid precursor protein-C42

2019 Spring National Meeting

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