(735b) Self-Assembly of Amyloid Peptide Fragments with Experiment Directed Simulations | AIChE

(735b) Self-Assembly of Amyloid Peptide Fragments with Experiment Directed Simulations


Amirkulova, D. - Presenter, University of Rochester
Chakraborty, M., University of Rochester
White, A., University of Rochester
Self-assembly of peptides and proteins is a relevant mechanism in biocompatible material design, microelectronics, drug design and pathogenesis. Amyloid peptides are a class of peptides that self assemble and are linked to neurodegenerative diseases, such as Alzheimer's, Parkinson's, Prion, and Huntington's diseases. Aβ42 is an amyloid peptide and its 10 residue long fragment is called Aβ21-10. This fragment is known to be a nucleation site for aggregation of Aβ42 to mature pathogenic fibers and it is stable in denaturing conditions. The intermolecular interactions that govern the structure and dynamics of this fragment are highly debatable currently. We used experiments and simulations to study the structure of Aβ21-10. We used experiment directed simulations (EDS) to bias the simulations with experimental Nuclear Magnetic Resonance spectroscopy results. EDS with the enhanced sampling technique Parallel Tempering Well-Tempered Ensemble improved sampling. Following enhanced sampling, separate EDS simulations were performed to investigate the dynamics and structure of this fragment. Diffusion constant and correlation functions were computed and compared to experimental results. We investigated the self-assembly of Aβ21-10 with simulations and compared the predicted results to experiments. Preliminary results from coarse graining multiple chains of Aβ21-10 will be discussed.