title: Visualizing gaussian-chain like structural models of human α-synuclein in monomeric pre-fibrillar state: Solution SAXS data and modeling analysis
creator: Dey, Madhumita
creator: Gupta, Arpit
creator: Badmalia, Maulik D
creator: Ashish, 
creator: Sharma, Deepak
description: 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.
publisher: Elsevier BV
date: 2025-02
type: Article
type: NonPeerReviewed
identifier:   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.      
relation: http://crdd.osdd.net/open/3217/