A multispectral study and computer simulation on the interaction of pomalidomide with human serum albumin

Abstract

Pomalidomide (POM) has been discovered as a new molecular-glue-type degraders in recent years. It is a potent immunomodulatory drug and is used for the treatment of recrudescent and intractable multiple myeloma (MM). The interaction between POM and human serum albumin (HSA) was studied by multiple spectral techniques, molecular docking technique, and molecular dynamics simulation in this research. POM and HSA formed a complex with one binding stoichiometry. Site I was the binding site of POM to HSA and the binding constant was (6.180 ± 0.009) × 103 M−1 (293 K). Based on the thermodynamic results, the binding process was exothermic and spontaneous. Van der Waals forces and H-bonds were the chief driving forces. The conformational changes in HSA induced by POM were reflected in β-turn content increasing and α-helix content reducing. The results of computer simulation were consistent with that of the multiple spectral experiments. In addition, the results of molecular docking indicated π electrons in POM were also vital for the stability of HSA-POM complex. Molecular dynamics simulation showed that Leu198, Lys199 and Trp214 played a contributing role in the binding process, and the fluorescence of HSA quenched by POM might be attributed to the reduction in the accessible surface area values of Trp214. This research is aimed at better understanding the effects of molecular-glue-type degraders on human health, and it is helpful in clinical treatment of MM.