Molecular dynamics simulation of the aggregation and folding mechanism of α-synuclein 47-56 in core peptide fragments induced by α-synuclein pentamer template.
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引用次数: 0
Abstract
The misfolding of intrinsically disordered α-synuclein protein, which can form β-sheet-rich fibrillar amyloid structures, is closely associated with Parkinson's disease (PD). The peptide α-synuclein 47-56 has been identified as the toxic core of α-synuclein and plays a pivotal role in the aggregation and misfolding processes of this protein. Investigating the template induction behavior of this peptide is crucial for elucidating the molecular mechanisms underlying α-synuclein misfolding and aggregation. To explore the molecular mechanism of the peptide α-synuclein 47-56, guided by the α-synuclein pentamer template, we conducted a 400 ns molecular dynamics simulation. In this simulation, the peptide α-synuclein 47-56 was positioned on both sides of the α-synuclein pentamers. Our results demonstrate distinct elongation characteristics of the peptide α-synuclein 47-56 on the two sides of the pentamer. The β-sheet structure readily formed on the left side of the α-synuclein pentamer, facilitating template induction. In contrast, the formation of β-sheet secondary structures was hindered on the right side of the α-synuclein pentamer. Furthermore, our analysis reveals that hydrogen bonding, electrostatic interactions, and van der Waals forces between the α-synuclein pentamer and monomer are crucial for β-sheet extension. Notably, we identified the α-synuclein 49-53 region as a key peptide segment in this process.
期刊介绍:
The Journal of Biomolecular Structure and Dynamics welcomes manuscripts on biological structure, dynamics, interactions and expression. The Journal is one of the leading publications in high end computational science, atomic structural biology, bioinformatics, virtual drug design, genomics and biological networks.