Exploring the binding interaction between bovine serum albumin and perindopril as well as influence of metal ions using multi-spectroscopic, molecular docking and DFT calculation

Abstract

The binding characteristics of BSA with perindopril, a third-generation angiotensin-converting enzyme inhibitor, was investigated using various spectroscopic approaches combined with molecular simulation including molecular docking and density functional theory calculation. Meantime, the influence of some trace metal ions on the binding characteristics of BSA with perindopril was investigated. The findings indicated the perindopril quenched BSA fluorescence in a static way. The values of binding site (n) and binding constant (Kb) of perindopril on BSA were close to 1 and 8.12 × 103 M−1 at 298 K, respectively, indicating that the binding affinity was moderate and the stoichiometric ratio of the perindopril-BSA complex was 1:1. Thermodynamic analysis results revealed that the ΔG0, ΔH0, and ΔS0 values were negative, demonstrating the binding interaction was a spontaneous and exothermic process, the interaction forces were mainly hydrogen bonds and van der Waals forces. The results of the replacement experiments and molecular simulations indicated that perindopril bound to the groove between sub-domain IIB and IIA. Furthermore, the results also revealed the BSA conformation altered slightly during binding with perindopril and the existence of transition metal ions would result in the increase in the Kb value of perindopril on BSA, resulting in the decline in the concentration of free perindopril. The frontier molecular orbitals and other quantum chemical parameters as well as conformation of perindopril in BSA complex obviously altered for forming the more stable perindopril-BSA complex.