Missense Mutations Modify the Conformational Ensemble of the α-Synuclein Monomer Which Exhibits a Two-Phase Characteristic.

ABSTRACT: α-Synuclein is an intrinsically disordered protein occurring in different conformations and prone to aggregate in β-sheet structures, which are the hallmark of the Parkinson disease. Missense mutations are associated with familial forms of this neuropathy. How these single amino-acid substitutions modify the conformations of wild-type α-synuclein is unclear. Here, using coarse-grained molecular dynamics simulations, we sampled the conformational space of the wild type and mutants (A30P, A53P, and E46K) of α-synuclein monomers for an effective time scale of 29.7 ms. To characterize the structures, we developed an algorithm, CUTABI (CUrvature and Torsion based of Alpha-helix and Beta-sheet Identification), to identify residues in the α-helix and β-sh

SUBMITTER: Guzzo A 

PROVIDER: S-EPMC8667727 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature