TY  - JOUR
ID  - open3217
UR  - http://crdd.osdd.net/open/3217/
IS  - 138614
A1  - Dey, Madhumita
A1  - Gupta, Arpit
A1  - Badmalia, Maulik D
A1  - Ashish, 
A1  - Sharma, Deepak
Y1  - 2025/02//
N2  - Here, using small angle X-ray scattering (SAXS) data profile as reference, we attempted to visualize conformational ensemble accessible prefibrillar monomeric state of ?-synuclein in solution. In agreement with previous reports, our analysis also confirmed that ?-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 C? 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 ?-helical content best-represents non-associating monomeric ?-synuclein.
PB  - Elsevier BV
JF  - Int. J. Biol. Macromol.
VL  - 288
KW  - ALPHAFOLD2; EOM; Monomer; Normal mode analysis; Protein structure; SAXS; ?-Synuclein
TI  - Visualizing gaussian-chain like structural models of human ?-synuclein in monomeric pre-fibrillar state: Solution SAXS data and modeling analysis
ER  -