Study On The Interaction Of Bovine Serum Albumin With Atorvastatin Calcium And Lisinopril

In this paper, spectroscopy combined with molecular simulation have been used to study the interaction of bovine serum albumin(BSA) with Atorvastatin Calcium(AC) and lisinopril, respectively. A series of key parameter have been detective to clarify the interaction mechanism of BSA with drugs as well as the binding model and three-dimensional space conformation of these BSA-drug complexes.Fluorescence spectroscopy is successful used to investigate the parameters of interaction of BSA with AC and lisinopril such as fluorescence quenching mechanisms, the number of binding sites, apparent binding constant, thermodynamic parameters and binding model. The driving forces of BSA with these two drugs binding process are calculated based on large numbers of experimental data. The results indicated that both the processes are enthalpy driven.The synchronous fluorescence spectroscopy and circular dichroism are used to investigate the BSA conformational changes in presence and absence of AC and lisinopril. Results shows that BSA secondary structure changes slightly and a-helix content decreased, but not of lisinopril. UV spectra and fluorescence spectra are used to calculate the distance between Trp residues of BSA and AC, lisinopril, respectively. It’s a clear case of energy transfer that occurred between BSA and AC(1.45nm) according to results, and so does lisinopril(1.98nm).In addition, the stereostructure of AC and lisinopril are optimized in Gaussian03W with different theoretical methods and basis set. Choosing the suitable function and basis set to optimize drugs after testing stability, investigating whether there is internal instability or spin contamination. Heat of formation, imaginary frequency, bond energy and bond angle are chosen to judge the end of optimization.The interaction of BSA with AC and lisinopril is simulated by AutoDock4.2after optimizing in Gaussian03W, exploring these two drugs specific recognition on BSA. The results show that AC binds within the site I of BSA while lisinopril within the site II, which is consistent with the experiment. Further analysis can be seen hydrogen bonds between residues and AC or lisinopril. That indicates the main interaction forces are hydrogen bonding, van der Waals forces.