Issue 35, 2024

Energy gap of conformational transition related with temperature for the NACore of α-synuclein

Abstract

Pathological aggregation of α-synuclein (α-syn) into amyloid fibrils is a major feature of Parkinson's disease (PD). The self-assembly of α-syn is mainly governed by a non-amyloid-β component core (NACore). However, the effects of concentrations and temperatures on their conformational transition remain unclear. To answer this question, we investigated the aggregation kinetics of NACore oligomers in silico by performing several independent all-atom molecular dynamics simulations. The simulation results show that tetramers are more prone to form β-sheets at 300 K than dimers and octamers. We also found that the NACore oligomers had higher β-sheet and β-barrel contents at 310 K. The inter-chain hydrophobic interactions, the backbone hydrogen bonding, the residue-residue interactions between V70–V77 as well as V77–V77 play important roles in the aggregation tendency of NACore octamers at 310 K. Interestingly, the energy gap analysis revealed that the conformational transition of NACore oligomers from intermediate states (β-barrel conformation) to stable structures (β-sheet layers) was dependent on the temperatures. In short, our study provides insight into the kinetic and thermodynamic mechanisms of the conformational transition of NACore at different concentrations and temperatures, contributing to a better understanding of the aggregation process of α-syn in Parkinson's disease.

Graphical abstract: Energy gap of conformational transition related with temperature for the NACore of α-synuclein

Supplementary files

Article information

Article type
Paper
Submitted
23 May 2024
Accepted
12 Aug 2024
First published
13 Aug 2024

Phys. Chem. Chem. Phys., 2024,26, 23062-23072

Energy gap of conformational transition related with temperature for the NACore of α-synuclein

P. Xia, Y. Cao, Q. Zhao and H. Li, Phys. Chem. Chem. Phys., 2024, 26, 23062 DOI: 10.1039/D4CP02131B

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