A Computational Investigation of Curcumin Glucoside in α-Synuclein Aggregation: DFT Characterization, Molecular Docking, and Secondary Data Analysis

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the aggregation of α-synuclein into oligomers and amyloid fibrils. Curcumin glucoside has been investigated as a potential inhibitor of α-synuclein aggregation; however, understanding its electronic properties and predicted interactions with α-synuclein fibrils may provide additional insights into its potential molecular behavior. This study integrates density functional theory (DFT) calculations, molecular docking, and quantitative analysis of previously published Thioflavin-T (ThT) fluorescence data to investigate the physicochemical properties and potential anti-aggregation effects of curcumin glucoside. DFT calculations were performed on isolated curcumin and curcumin monoglucoside molecules using the B3LYP-D3(BJ)/def2-SVP level of theory with implicit aqueous solvation. The HOMO–LUMO energy gaps were 3.626 eV for curcumin and 3.372 eV for curcumin monoglucoside, while their dipole moments were 7.53 D and 11.19 D, respectively. These differences indicate changes in the electronic structure and molecular polarity associated with glucosylation. Molecular docking against selected α-synuclein fibril structures representing different disease stages showed docking scores ranging from −5.1 to −6.7 kcal/mol for curcumin and from −6.2 to −6.6 kcal/mol for curcumin glucoside. Previously published ThT fluorescence data related to curcumin glucoside were analyzed using a four-parameter logistic (4PL) model to characterize the reported aggregation-response profiles over time. The combined findings provide complementary electronic-structure, docking, and aggregation-kinetic perspectives on curcumin glucoside. Importantly, the DFT calculations were restricted to isolated molecules and did not evaluate electron redistribution, charge-transfer pathways, or reaction energetics within protein–ligand complexes. The docking scores are computational estimates from a scoring function and are not experimentally measured binding affinities. The 4PL analysis is a secondary re-examination of previously published ThT fluorescence data and does not constitute new experimental validation of aggregation inhibition. Collectively, these results supply a computational and quantitative descriptive basis that can guide further experimental and higher-level quantum-chemical investigation of curcumin glucoside as a potential modulator of α-synuclein aggregation; they do not, by themselves, establish a quantum-mechanical mechanism of action.