Determination of interactions between human serum albumin and niraparib through multi-spectroscopic and computational methods

Abstract The interactions between 2-{4-[(3 S )-piperidin-3-yl] phenyl}-2H-indazole-7-carboxamide (niraparib) and human serum albumin (HSA) were investigated through fluorescence and computational studies. Fluorescence experiments showed that the static quenching mechanism and the binding constant of the HSA–niraparib system at a single binding site was approximately 4 × 10 4  L mol −1 . Thermodynamic constants indicated that the binding of niraparib to HSA was mainly driven by electrostatic interactions. Competition experiments and molecular docking simulations revealed that niraparib bound to site III of HSA. Synchronous fluorescence and Fourier transform infrared spectroscopy (FT-IR) results suggested that interactions between niraparib and HSA could affect the conformation and microenvironment of HSA. Circular dichroism (CD) measurements revealed that the α-helix contents of HSA negligibly increased after binding with niraparib. Molecular dynamics simulations demonstrated the stability of the binary HSA–niraparib system and confirmed that electrostatic forces accounted for the dominant contribution to system energy between HSA and niraparib.