http://crdd.osdd.net/open/id/eprint/3217 2026-02-02T07:16:35Z info:eu-repo/semantics/descriptiveMetadata Visualizing gaussian-chain like structural models of human α-synuclein in monomeric pre-fibrillar state: Solution SAXS data and modeling analysis Dey, Madhumita Gupta, Arpit Badmalia, Maulik D Ashish, Sharma, Deepak 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. Elsevier BV 2025-02 Article NonPeerReviewed Dey, Madhumita and Gupta, Arpit and Badmalia, Maulik D and Ashish, and Sharma, Deepak (2025) Visualizing gaussian-chain like structural models of human α-synuclein in monomeric pre-fibrillar state: Solution SAXS data and modeling analysis. Int. J. Biol. Macromol., 288 (138614). p. 138614. http://crdd.osdd.net/open/3217/ info:eu-repo/semantics/humanStartPage