Artificial Intelligence-Aided Virtual Screening and Molecular Dynamics Analysis of Novel Xanthine Oxidase Inhibitory Peptides Derived from Sunflower ( Helianthus annuus ) Proteins

Gout is an inflammatory arthritis caused by urate crystal accumulation, and discovering natural xanthine oxidase (XO) inhibitors from food and agricultural sources is of growing interest. In this study, we employed AI-driven virtual screening to identify XO inhibitory peptides from sunflower (Helianthus annuus) proteins. Screening 29,100 sequences with the ConPLex algorithm, we identified two peptides, LCAFNK and LIFCEK, with IC50 values of 28.06 and 20.32 mM, respectively. Gaussian accelerated molecular dynamics simulations revealed that LCAFNK acts as a competitive inhibitor by inducing conformational opening of the F163-E200 region, while LIFCEK likely exerts noncompetitive inhibition by affecting electron transport and substrate binding stability. Both peptides also demonstrated significant antioxidant activities against DPPH and ABTS radicals. These findings highlight sunflower proteins as a valuable source of natural XO inhibitors with antioxidative benefits, providing new opportunities for functional food development targeting gout management.