Study On The Interaction Of Bovine Serum Albumin With Angiotensin Converting Enzyme Inhibitors

In this paper, the spectrum methods and computer simulation techniques were introduced to study the mechanism of interaction between ACEI and Bovine Serum Alblumin(BSA). The former represents and affirms the key parameters to the interaction, the latter explores the ACEIs and BSA binding force and their three-dimensional conformation at the molecular level and predicts the origin of the interaction.Firstly, with Fluorescence Spectroscopy, series of key parameters of interaction between BSA and ACEIs were successfully studied, including Quenching mechanism, Binding constant, Number of binding site n, Binding site, Thermodynamic constant, Binding force etc. And the driving forces of BAS and the four drugs binding processes are calculated based on abundant experimental data. The results indicate that all of the processes are enthalpy driven.Secondly, the conformational changes were investigated by jointing Synchronous fluorescence spectroscopy, Circular dichroism, Infrared Spectroscopy and Ultraviolet spectroscopy, in presence and absence of ACEIs. Results show that BSA secondary structure changes slightly and α-helix content is decreased.Finally, the stereostructure of ACEIs are optimized by Gaussian 03 W with different theoretical methods and basis set, and would be checked by frequency to ensure the correctness. And the BSA crystal structure would be optimized in water and NaCl by NAMD, to make BSA closer to the natural conformation. After optimizing, the interactions between BSA and ACEIs are simulated by AutoDock 4.2, to explore these drugs specific recognition on BSA. The results show that ACEIs binds within the site I of BSA, which is consistent with the experiment. Further analysis can be seen from hydrogen bonds between residues and ACEIs. That indicates the main interaction forces are hydrogen bonding, van der Waals forces.