Molecular Dynamics Study of α-Synuclein Domain Deletion Mutant Monomers.

ABSTRACT: Aggregates of misfolded α-synuclein proteins (asyn) are key markers of Parkinson's disease. Asyn proteins have three domains: an N-terminal domain, a hydrophobic NAC core implicated in aggregation, and a proline-rich C-terminal domain. Proteins with truncated C-terminal domains are known to be prone to aggregation and suggest that understanding domain-domain interactions in asyn monomers could help elucidate the role of the flanking domains in modulating protein structure. To this end, we used Gaussian accelerated molecular dynamics (GAMD) to simulate wild-type (WT), N-terminal truncated (ΔN), C-terminal truncated (ΔC), and isolated NAC domain asyn protein variants (isoNAC). Using clustering and contact analysis, we found that removal of the N-terminal domain led to increased contacts betw

SUBMITTER: Onishi N 

PROVIDER: S-EPMC10996548 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature