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

α -Glucosidases catalyze the hydrolysis of the α -glucosidic bond located at the non-reducing ends of substrates, resulting in the release of glucose. α -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 α -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 α -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 α -glucosidase, which has practical value for the future design and development of C. oleifera polysaccharides as hypoglycemic drugs. Various molecular dynamics simulation techniques were utilized to investigate the precise binding characteristics and transport mechanism of Camellia oleifera polysaccharides in α-glucosidase. The significance of Arg200 and Arg400 in the stable attachment of Camellia oleifera polysaccharide was recognized, and it was established that electrostatic and hydrogen bonding interactions are pivotal in the binding of polysaccharides. A unique mode of transport for Camellia oleifera polysaccharide, dependent on hydrogen bonding and extensively involving Asp333, was identified. [ABSTRACT FROM AUTHOR]