Exploration of the Interactions between Maltase–Glucoamylase and Its Potential Peptide Inhibitors by Molecular Dynamics Simulation

Diabetes mellitus, a chronic metabolic disorder, represents a serious threat to human health. The gut enzyme maltase–glucoamylase (MGAM) has attracted considerable attention as a potential therapeutic target for the treatment of type 2 diabetes. Thus, developing novel inhibitors of MGAM holds the promise of improving clinical management. The dipeptides, Thr-Trp (TW) and Trp-Ala (WA), are known inhibitors of MGAM; however, studies on how they interact with MGAM are lacking. The work presented here explored these interactions by utilizing molecular docking and molecular dynamics simulations. Results indicate that the active center of the MGAM could easily accommodate the flexible peptides. Interactions involving hydrogen bonds, cation-π, and hydrophobic interactions are predicted between TW/WA and residues including Tyr1251, Trp1355, Asp1420, Met1421, Glu1423, and Arg1510 within MGAM. The electrostatic energy was recognized as playing a dominant role in both TW-MGAM and WA-MGAM systems. The binding locations of TW/WA are close to the possible acid-base catalytic residue Asp1526 and might be the reason for MGAM inhibition. These findings provide a theoretical structural model for the development of future inhibitors.