Molecular Dynamics Study on the Binding Characteristics and Transport Mechanism of Polysaccharides with Different Molecular Weights in Camellia Oleifera Abel.

Abstract

[Formula: see text]-Glucosidases catalyze the hydrolysis of the [Formula: see text]-glucosidic bond located at the non-reducing ends of substrates, resulting in the release of glucose. [Formula: see text]-glucosidase is an important drug target for controlling type 2 diabetes. Previous studies have shown that polysaccharide isolated and purified from Camellia oleifera Abel exhibits hypoglycemic properties. In this study, the mode in which the polysaccharide binds and the associated binding free energy, as well as the release mechanism dependent on hydrogen bonding, has been elucidated through the integration of multiple molecular dynamic simulations. Residues Arg200 and Arg400 located at the active site of [Formula: see text]-glucosidase play a major role in polysaccharide binding, primarily through electrostatic and hydrogen-bonding interactions. The optimal route for the transportation of polysaccharides has been identified, and a comprehensive analysis of the thermodynamic and kinetic characteristics has been discussed through the application of umbrella sampling techniques. The dynamic delivery properties of [Formula: see text]-glucosidase suggest that the energy barrier necessary for the escape of disaccharides is approximately 12 kcal/mol. This barrier primarily arises from the interactions of hydrogen bonding and electrostatic interactions. The results of this study provide a basic understanding of the ligand transport mechanism based on the environment of [Formula: see text]-glucosidase, which has practical value for the future design and development of C. oleifera polysaccharides as hypoglycemic drugs.