Investigation of the interaction between glucose-6-phosphate dehydrogenase and ATA-inhibitor by molecular docking and molecular dynamics simulation

Abstract

Human glucose-6-phosphate dehydrogenase (G6PD) is a kind of polymerase, which can bind cofactors β-D-glucose-6-phosphate (G6P) and catalyzes NADP+ to produce NADPH. Therefore, G6PD plays a crucial role in maintaining reduced glutathione to protect cells from oxidative stress disorders. Aurine tricarboxylic acid (ATA) is a potential metal binding inhibitor. Here, we found that G6P and ATA have a common potential binding site in the G6PD receptor conformation through molecular docking. The results of molecular dynamics (MD) simulation showed that, compared with apo-G6PD, G6P-G6PD and ATA-G6PD had lower root mean square deviation (RMSD), radius of gyration (Rg), and solvent accessible surface area (SASA), indicating that binding ligand molecules could promote the overall conformation of G6PD to be more stable. These results suggest that ATA may compete for the binding sites of G6P, thereby inhibiting the catalytic function of G6PD. This study revealed the mechanism of interaction between ATA inhibitors and G6PD at the atomic conformation level, providing a theoretical basis for investigating the effects of cellular oxidative stress.