The 29th Annual International Symposium on Computational Science and EngineeringよりANSCSE29 Poster Presentation Awardを受賞しました。(複雑系科学専攻 Prin Tadawattana D1)

Toshifumi Mori
Norio Yoshida

Elucidation of the Role of ATP in the Liquid-Liquid Phase Separation of α-synuclein

Parkinson’s disease (PD) and other synucleinopathies are associated with the liquid-liquid phase separation (LLPS) of α-synuclein into insoluble fibrils forming Lewy bodies (LBs) and Lewy neurites (LNs). Recent experimental studies have suggested that the liquid-to-solid transition of α-synuclein may involve the formation of amyloid-containing aggregates; however, the molecular understanding this process remains unclear. Herein, molecular dynamic (MD) simulations of five α-synuclein systems, ranging from monomer to pentamer, were performed for the NAC region were performed to investigate the oligomerization phenomena by evaluating the structural stability, intermolecular association, and residue-level interactions. The results indicate that the tetrameric assemblies exhibit transient oligomeric behavior, whereas the pentamer maintains a more persistent and dynamically stable intermolecular interactions throughout the simulation. Radius of gyration analysis shows that structural compactness of pentamer remains stable over time, suggesting that it retains relatively stable β-sheet characteristics based on secondary structure analysis. In addition, intermolecular contacts at the residue level reveal key interaction localized within the flexible disordered region (residues 18-28), implying that this segment may function as an important bridging region during oligomer formation. Overall, these findings propose that the early stages of α-synuclein oligomerization is influenced by oligomer size and dynamic intermolecular interactions within disordered regions, providing molecular insight into the initial aggregation process prior to mature fibril formation.