Molecular Dockings and Molecular Dynamics Simulations Reveal the Potency of Different Inhibitors against Xanthine Oxidase

[Image: see text] Xanthine oxidase (XO), which can catalyze the formation of xanthine or hypoxanthine to uric acid, is the most important target of gout. To explore the conformational changes for inhibitor binding, molecular dockings and molecular dynamics simulations were performed. Docking results indicated that three inhibitors had similar pose binding to XO. Molecular dynamics simulations showed that the binding of three inhibitors influenced the secondary structure changes in XO. After binding to the inhibitor, the peptide Phe798-Leu814 formed different degrees of unhelix, while for the peptide Glu1065-Ser1075, only a partial helix region was formed when allopurinol was bound. Through the protein structure analysis in the simulation process, we found that the distance between the active residues Arg880 and Thr1010 was reduced and the distance between Glu802 and Thr1010 was increased after the addition of inhibitors. The above simulation results showed the similarities and differences of the interaction between the three inhibitors binding to the protein. MM-PBSA calculations suggested that, among three inhibitors, allopurinol had the best binding effect with XO followed by daidzin and puerarin. This finding was consistent with previous experimental data. Our results can provide some useful clues for further gout treatment research.