In this study, the interactions of a series of benzofuran derivatives with bovine serum albumin (BSA) were investigated using UV–Vis and fluorescence spectroscopy and molecular modeling. The intrinsic fluorescence of BSA was found to be quenched by the benzofuran derivatives. The binding constants between the benzofuran derivatives and BSA calculated from fluorescence quenching were found to be (1.80 ± 0.04) 9 104, (1.88 ± 0.06) 9 104, and (2.02 ± 0.07) 9 104 dm3 mol-1, respectively. According to the fluorescence resonance energy transfer, the average binding distances between the benzofuran derivatives and BSA were calculated to be 3.22, 3.29, and 3.02 nm, respectively. The binding of the benzofuran derivatives and BSA was modeled by molecular docking and molecular dynamic (MD) simulation methods. Principal component analysis was performed on 2001 snapshots of the MD trajectories at the equilibrium state. Based on the different regions in the PC space, about 15 conformations were selected, and the average of these was used to determine the interactions between the benzofuran derivatives and BSA. The results revealed that the benzofuran derivatives preferred the binding pocket of domain II of BSA.
