TOWARD UNDERSTANDING AMYLOIDOSIS: ALL-ATOM MOLECULAR DYNAMICS SIMUALTIONS OF AM

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Amyloidosis has been linked to many human diseases, including Alzheimers, Huntingtons and Parkinsons and the transmissible spongiform encephalopathies (prion diseases), type II diabetes that affect large human population. A common pathological process shared by all these diseases is transformation of normal proteins to beta-sheet dominated fibrillar protein aggregates. An enhanced understanding of the molecular events in beta-sheet mediated aggregation is needed to design and implement effective inhibition and refolding strategies, improve folding yields, and design therapeutic inhibitors. We propose to study how peptides assemble to form ordered oligomers that lead to amyloid fibrils by all-atom molecular dynamics simulations. We will use small peptide fragments as the model systems to investigate the early stage formation of the amyloid protofibrils and their interactions with inhibitors.