%0 Journal Article
%A Dey, Madhumita
%A Gupta, Arpit
%A Badmalia, Maulik D
%A Ashish, 
%A Sharma, Deepak
%D 2025
%F open:3217
%I Elsevier BV
%J Int. J. Biol. Macromol.
%K ALPHAFOLD2; EOM; Monomer; Normal mode analysis; Protein structure; SAXS; α-Synuclein
%N 138614
%P 138614
%T Visualizing gaussian-chain like structural models of human α-synuclein in monomeric pre-fibrillar state: Solution SAXS data and modeling analysis
%U http://crdd.osdd.net/open/3217/
%V 288
%X Here, using small angle X-ray scattering (SAXS) data profile as reference, we attempted to visualize conformational ensemble accessible prefibrillar monomeric state of α-synuclein in solution. In agreement with previous reports, our analysis also confirmed that α-synuclein molecules adopted disordered shape profile under non-associating conditions. Chain-ensemble modeling protocol with dummy residues provided two weighted averaged clusters of semi-extended shapes. Further, Ensemble Optimization Method (EOM) computed mole fractions of semi-extended ``twisted'' conformations which might co-exist in solution. Since these were only Cα traces of the models, ALPHAFOLD2 server was used to search for all-atom models. Comparison with experimental data showed all predicted models disagreed equally, as individuals. Finally, we employed molecular dynamics simulations and normal mode analysis-based search coupled with SAXS data to seek better agreeing models. Overall, our analysis concludes that a shifting equilibrium of curved models with low α-helical content best-represents non-associating monomeric α-synuclein.