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Amyloid-beta (A$\beta$ ) peptides are 36 to 43 amino acid residues, implicated by the amyloid cascade hypothesis as one of the cause of Alzheimer’s disease (AD). In the brain, A$\beta$ forms small peptide aggregates, called oligomers, leading to $\beta$-sheet fibrils that, with time, forms the 3D amyloid plaque that is the hallmark of AD. The structure of fibrils consists of parallel and/or anti-parallel sheets wound in a wide array of complex three-dimensional structures. Though parallel $\beta$-sheets are more common in AD, anti-parallel sheets are believed by some researchers to be associated with early onset AD.
This paper presents our effort in building a coarse-grained model of the formation of micro-crystal fibril of fragments of A$\beta$. For computational efficiency, an amino acid is represented as a spherical bead, located at the center of its C$_\alpha$ carbon.This allows the study of systems of up to 200 peptides. In the spirit of Go models, the intra-peptide dihedral and van der Waals interactions, as well as inter-peptide interactions are biased to the experimental crystal structures. Two C$_\alpha$ beads on different peptides can also interact by a Mercedes-Benz-type hydrogen bond,which stabilizes $\beta$-sheet. MD simulations observed that A$\beta$ fragment models that are biased to anti-parallel $\beta$-sheets condensed to fibrils at lower temperature than models biased to parallel $\beta$-sheets. Finally the kinetics of fibril formations are presented, and the implication to AD are discussed.
