Intermolecular Interaction Of Steroid Hormones With Bovine Serum Albumin:Spectroscopic And Molecular Docking Methods

Protein is the basis of all living matter. As the most abundant carrier protein in the plasma, serum albumin is not only essential for physiological functions but also plays an important role in the storage and transportation for most of the endogenous substances and exogenous substances. Therefore, the study on the interaction between drug and the protein is useful for understanding of the mechanism and metabolic processes and it offered theoretical basis of the other relevant research field just like clinical medicine and life science.Recently, steroid hormones have been widely used because of its numerous pharmacological activities including anti-inflammatory and immunosuppression and anti-allergic. In this study, we respectively reported the interactions of bovine serum albumin (BSA) with two kinds of steroidal drugs such as prednisolone and megestrol acetate by spectroscopic and molecular docking methods under simulated physiological condition (pH=7.4). The experimental results showed the interaction information of steroid hormones with BSA. is useful for reforming drug structure and synthetizing new drugs. The main process and achievements of this paper are as follow:1. Quenching rate constant (Kq),the binding constants (K) and the binding distance (r) between those two kinds of steroid hormones and BSA at different temperatures were calculated according to the data obtained from fluorescence titration, respectively. With the increasing temperature, the decreasing value of Kq and K indicated that the probable quenching process is static quenching mechanism. The thermodynamic parameters showed that Van der Waals and hydrogen bonding interactions played a major role in the binding interaction. On the basis of site marker competition experiments, it was considered that prednisolone binds with BSA in the hydrophobic pocket of site Ⅱ (subdomain ⅢA), as well as megestrol acetate.2. According to the results of circular dichroism measurements and synchronous fluorescence spectroscopy, the micro-environment surrounding Tyr and Trp residues has slight change in the presence of prednisolone, as well as megestrol acetate. Both of the steroidal drugs would increase the α-helical content of BSA increased, it indicated that the steroid hormone drugs-BSA complex induced some conformational changes in BSA.3. Molecular docking method was used to simulate the interaction between steroid hormones and BSA. It showed that the fluorescence of BSA had been quenched with both of prednisolone and megestrol acetate through the the Van der Waals force and hydrogen bond formation in site Ⅱ. In addition, the steroid hormones-BSA complex had stable free energy of binding, which was in accordance with the results of spectroscopic measurement. Moreover, the primary bond distances and angles of the small molecules had been changed after docking.