Binding interaction of sorafenib with bovine serum albumin: Spectroscopic methodologies and molecular docking

Abstract

The binding interaction of sorafenib with bovine serum albumin (BSA) was studied using fluorescence, circular dichrosim (CD) and molecular docking methods. The results revealed that there was a static quenching of BSA induced by sorafenib due to the formation of sorafenib–BSA complex. The binding constant and number of binding site of sorafenib with BSA under simulated physiological condition (pH = 7.4) were 6.8 × 10⁴ M⁻¹ and 1 at 310 K, respectively. Base on the sign and magnitude of the enthalpy and entropy changes (ΔH⁰ = −72.2 kJ mol⁻¹ and ΔS⁰ = −140.4 J mol⁻¹ K⁻¹) and the results of molecular docking, it could be suggested that the binding process of sorafenib and BSA was spontaneous and the main interaction forces of sorafenib with BSA were van der Waals force and hydrogen bonding interaction. From the results of site marker competitive experiments and molecular docking, it could be deduced that sorafenib was inserted into the subdomain IIA (site I) of BSA and leads to a slight change of the conformation of BSA. And, the significant change of conformation of sorafenib occurred in the binding process with BSA to increase the stability of the sorafenib–BSA system, implying that the flexibility of sorafenib played an important role in the binding process.