司美格鲁肽与人血清白蛋白相互作用模式及亲和力OA

Objective This study comprehensively employed computer simulation molecular docking technology and surface plasmon resonance(SPR)technology to investigate the interaction between semaglutide and human serum albumin(HSA).Methods Molecular docking simulations were conducted using two software tools,Autodock Vina and Discovery Studio(DS),to reveal the structural interaction pattern between semaglutide and HSA,identifying the binding site and key amino acid residues.Additionally,to address the limitations of traditional SPR analysis methods,an innovative approach was proposed,using semaglutide as the conjugated ligand and single-cycle kinetics as the analytical method.Results In the Autodock Vina and Discovery Studio docking simulations,the affinity scores between semaglutide and HSA were-66.88 and-24.24 kJ•mol-1,respectively,indicating strong interactions.Furthermore,in the SPR-based analysis,the sensor plots from multi-cycle kinetics and single-cycle kinetics experiments both aligned with the kinetic model.Using the 1∶1 Langmuir kinetic model to fit the curves,no significant difference was observed in the binding affinity of semaglutide to HSA between the two manufacturers.Conclusions The improved SPR analysis method can measure the binding affinity more accurately and is highly consistent with the results of molecular simulation.It provides a new technical means and theoretical basis for the development of GLP-1 analogues.