Impact of Phosphorylation on the Structural Ensemble of alpha-Synuclein in Aqueous Solution

Serine 129 can be phosphorylated in pathological inclusions formed by the intrinsically disordered protein α -synuclein (AS), a key player in Parkinson’s disease and other synucleinopathies. Here, molecular simulations suggest that phosphorylation does not impact on the structural ensemble of the physiological AS conformational ensemble in aqueous solution, as the phosphate group is mostly solvated. Our findings are consistent with experimental data, with the caveat that the latter are carried out on the non-acetylated, non-physiological form of the protein. These findings shed light into the molecular implications of AS phosphorylation and this may open novel perspectives for therapeutic intervention. ### Competing Interest Statement The authors have declared no competing interest.