The Oxidative Process of Acarbose, Maysin, and Luteolin with Maltase-Glucoamylase: Molecular Docking and Molecular Dynamics Study

Abstract

Type 2 diabetes mellitus has been classified as the epidemic of the XXI century, making it a global health challenge. Currently, the commonly used treatment for this disease is acarbose, however, the high cost of this medicine has motivated the search for new alternatives. In this work, the maysin, a characteristic flavonoid from maize inflorescences, and its aglycon version, luteolin, are proposed as acarbose substitutes. For this, a theoretical comparative analysis was conducted on the molecular interactions of acarbose, maysin, and luteolin with human maltase-glucoamylase (NtMGAM), as well as their oxidative process. The binding energies in the active site of NtMGAM with acarbose, maysin, and luteolin molecules were predicted using a molecular docking approach applying the Lamarckian genetic algorithm method. Theoretical chemical reactivity parameters such as chemical hardness (η) and chemical potential (µ) of the acarbose, maysin, and luteolin molecules, as well as of the amino acids involved in the active site, were calculated using the electronic structure method called Density Functional Theory (DFT), employing the M06 meta-GGA functional in combination with the 6-31G(d) basis set. Furthermore, a possible oxidative process has been proposed from quantum-chemical calculations of the electronic charge transfer values (ΔN), between the amino acids of the active site and the acarbose, maysin, and luteolin. Molecular docking predictions were complemented with molecular dynamics simulations. Hence, it was demonstrated that the solvation of the protein affects the affinity order between NtMGAM and ligands.