TY  - JOUR
AU  - de Bruyn, Emile
AU  - Dorn, Anton Emil
AU  - Rossetti, Giulia
AU  - Fernandez, Claudio
AU  - Outeiro, Tiago F.
AU  - Schulz, Jörg B.
AU  - Carloni, Paolo
TI  - Impact of Phosphorylation on the Physiological Form of Human alpha-Synuclein in Aqueous Solution
JO  - Journal of chemical information and modeling
VL  - 64
IS  - 21
SN  - 1549-9596
CY  - Washington, DC
PB  - American Chemical Society
M1  - FZJ-2024-06053
SP  - 8215–8226
PY  - 2024
AB  - Serine 129 can be phosphorylated in pathological inclusions formed by the intrinsically disordered protein human α-synuclein (AS), a key player in Parkinson’s disease and other synucleinopathies. Here, molecular simulations provide insight into the structural ensemble of phosphorylated AS. The simulations allow us to suggest that phosphorylation significantly impacts the structural content of the physiological AS conformational ensemble in aqueous solution, as the phosphate group is mostly solvated. The hydrophobic region of AS contains β-hairpin structures, which may increase the propensity of the protein to undergo amyloid formation, as seen in the nonphysiological (nonacetylated) form of the protein in a recent molecular simulation study. Our findings are consistent with existing experimental data with the caveat of the observed limitations of the force field for the phosphorylated moiety.
LB  - PUB:(DE-HGF)16
C6  - 39462994
UR  - <Go to ISI:>//WOS:001344038800001
DO  - DOI:10.1021/acs.jcim.4c01172
UR  - https://juser.fz-juelich.de/record/1032184
ER  -