Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery: Bridging Experiments and Computations - September 10-14, 2014, Istanbul, Turkey

Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Poster Session II

82-POS Board 35 Computer Simulations on Amyloid Formation Seokmin Shin 1 , SeongByeong Park 1 , Soonmin Jang 2 , Kyunghee Lee 2 .

1 Seoul National University, Seoul, South Korea, 2 Sejong University, Seoul, South Korea. Computational studies can provide basic understanding concerning the detailed mechanism of amyloid formation, the formation of amyloid fibrils and prefibrilar aggregates of misfolded proteins and peptides. Understanding amyloid formation is very important to elucidate possible causes for various neurodegenerative disorders. Systematic replica exchange molecular dynamics simulations have been performed on the formation of the oligomers and protofibrils of Aβ peptide and peptides from α-synuclein. We also performed MD simulations on different structural models of such fibrils including the effects of mutations. The mechanism of aggregation and growth of these peptides is examined from detailed analysis of such simulations. It was shown that the steric zipper contacts provided favorable interactions in the aggregation process and the structural flexibility might play important role for enhancing aggregation. Our results suggested that amyloid formation is basically a hierarchical process and different topologies are favored in the different stages of aggregation. Self-assembly of peptide-based building blocks has been shown to be useful in constructing artificial bionanostructures. We performed MD simulations on the proposed nanoring structures formed by the self-assembly of β-sheet forming peptides. The stability of the nanoring structure with respect to the size is investigated and several factors contributing to the stability are examined. We have also demonstrated that the sizes of nanorings can be controlled by introducing selective mutations.

135