Solvent-dependent structural and dynamic behavior of α-gliadin in aqueous ethanol systems: Insights from molecular dynamics simulations.

Understanding the behavior of gliadin in mixed aqueous-organic solvents is vital for food material science. This study integrates advanced structure prediction with microsecond-scale molecular dynamics (MD) simulations to explore the conformational and solvation behavior of α-gliadin across ethanol-water mixtures. Our findings reveal that α-gliadin maintains structural stability across all solvent conditions, with a progressive increase in molecular expansion at higher ethanol concentrations. Ethanol promotes up to 30 % more salt bridges, enhances helical content, and reduces β-sheet formation. Residue-level flexibility analysis reveals that specific segments, such as Gln227-Ala261, Tyr121-Gln136, and the proline- and glutamine-rich region Pro64-Leu78, exhibit higher fluctuation, suggesting their sensitivity to solvent-induced conformational changes, whereas domains stabilized by electrostatic and covalent interactions remain rigid (show less fluctuation). Thermodynamic and PCA analyses highlight stronger protein-solvent interactions and greater conformational diversity at higher ethanol concentrations. This work provides a detailed molecular-level quantification of how ethanol modulates α-gliadin structure and solvation.