Glycation-mediated binding defect in human serum albumin transport oferdosteine: implications in diabetes

Human serum albumin (HSA) is a protein in human blood primarily responsible for transporting ligands. Erdosteine is an important drug used in the treatment of acute and chronic respiratory diseases. This study employed molecular docking and molecular dynamics simulation methods to investigate the interaction between erdosteine and HSA. In the presence of glucose, the binding energy of erdosteine decreased, indicating reduced binding affinity. Docking results suggested changes in the interaction sites and binding residues, with the preferential binding site shifting in the presence of glucose. Molecular dynamics simulations showed increased fluctuations when glucose was present. The solvent-accessible surface area of all HSA systems remained stable under physiological conditions, with a slight decrease over time. Analysis of secondary structural changes indicated stable erdosteine binding with no alteration in HSA's secondary structure. Hydrogen bonding analysis showed a decrease in hydrogen bond formation between erdosteine and HSA in the presence of glucose; since hydrogen bonding is crucial for ligand-protein interactions, this reduction is significant. Principal component analysis indicated that HSA's flexibility was not affected by erdosteine binding, even in the presence of glucose. Electrostatic interactions played a key role in erdosteine binding to HSA, with Arg 218 contributing the highest energy in the complex under glucose conditions. Elevated glucose levels in diabetic patients can induce structural and functional changes in proteins, potentially impacting the effective management of coexisting clinical conditions. Such changes may affect drug binding to transport proteins, thereby altering drug efficacy, clearance, and therapeutic outcomes.