A molecular dynamics simulations study of the ionic liquid effect on the β-glucosidase active site interactions with a flavonoid glycoside

Abstract

Since the ionic liquid (IL) media is an appropriate environment for the enzymatic extraction of glycosides from natural resources, a detailed molecular understanding of the effect of IL concentration on enzyme function, with a focus on enzyme-substrate interactions, is critical. The best docking pose of Quercetin-4′-O-beta-D-glucopyranoside (Q-4′) in the active site of the β-glucosidase (BGL) enzyme was determined using molecular docking methods. Since flavonoid glycosides and enzymes are soluble in imidazolium-based ILs, the aqueous 1-butyl-3-methylimidazolium chloride ([BMIM][Cl]) was used as a solvent in this study. The interactive residues of the BGL active site, as well as the types of interactions, in BGL–Q-4′ complex were then discovered using structural interaction fingerprints (SIFt) calculations. After that, the molecular perspective of the ionic liquid (IL) concentration effect on this complex and its interactions were simulated using 100 ns all-atom MD simulations. According to SIFt changes, changing the IL concentration influenced the overall interactions in the BGL–Q-4′ complex and involved residues. The RMSF findings indicated that the maximum flexibility of the interactive residues was observed in the 50% IL solution, however, flexibility changes were not high enough to alter enzyme activity. More analysis showed that solvent effects influenced hydrogen bond (HB) interactions with the substrate in both active site subsites; glycone (subsite -1) and aglycone subsites. Aromatic interactions followed a similar trend, suggesting that changes in IL concentration affected them. The solvent effects had a greater impact on the interactions with the aglycone part in both cases, which was attributed to aglycone subsite's greater solvent accessibility. Furthermore, it was found that IL concentration had a negative impact on the enzymatic hydrolysis process by influencing the formation of HB with Glu193 as well as the nucleophilic attack of Glu402. Finally, SDF findings indicated that an accumulation of IL molecules at the active site entrance could reduce enzyme activity by reducing the active site's accessibility to the substrate. By providing a molecular perspective on the BGL-substrate complex behavior in the IL system, our findings lead to a deeper understanding of the flavonoid glycoside hydrolysis process in these useful solvents.