Biomolecular Separations Research Group

A hallmark of Alzheimer's disease (AD) is the formation of extracellular peptide plaques between nerve cells in the brain. These plaques are formed from many proteins including amino acid fragments called Abeta (Aβ) peptide that aggregate together into toxic oligomers and fibrils. Although Aβ peptide is implicated in AD, the fundamental molecular mechanism for disease pathogenesis remains unclear. This has made it difficult to identify the key aspects of Aβ peptide neurotoxicity and treatment strategies. Furthermore, a set of mutations, A2T and A2V, in the N-terminal domain of the Aβ peptide have been identified as protective and causative, respectively. Combining the results from our and other labs, we provide a possible mechanistic path using in vitro experiments, reaction modeling and molecular dynamics of the biophysical properties of the protective and causative mutants. Additionally, the NMDA (N-methyl-D-aspartate) receptor has been a pharmacological target of various diseases including AD. With this in mind, our research focuses on the interaction between Aβ peptides and the NMDA receptor, using in silico methods- primarily  molecular docking and molecular dynamics simulations.