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Center for Nonlinear Studies |
The intrinsically disordered amyloid-β (Aβ) peptide is a major molecular player in Alzheimer’s disease. An in-depth understanding of the structure and dynamics of the peptide both in monomeric and aggregate form is crucial for designing new therapeutic approaches. In the first of the talk, I will talk about how Aβ42 monomer structures get affected by addition of nitroxide spin labels during paramagnetic relaxation enhancement (PRE) experiments. Through comparison of computationally generated structural ensembles, we show that the tagged peptide induces a strong population shift in a subset of the original Aβ42 structural sub-populations. Our results suggest that PRE experiments, which are commonly used to probe into long-range dynamics of Aβ peptides, should be carefully interpreted using additional experiments and molecular simulations. In the second part, we study the nucleation and elongation mechanisms of the diseased polymorph of the Aβ fibril using an off-lattice coarse-grained protein model. Our model shows that the lock-and-dock mechanism is the dominant mechanism for fibril elongation by monomer addition.
Host: William S. Hlavacek (T-6)