Molecular Docking And Molecular Dynamic Simulation Studies For Adenosine Deaminase Inhibitors As Therapeutic Targets

Adenosine deaminase (EC, 3.5.4.4), is a metalloenzyme that contains a zinc ion. This enzyme plays a key role in purine metabolism and irreversible hydrolysis of adenosine and 2´-deoxy adenosine to inosine, 2´-deoxy inosine and ammonia. Adenosine deaminase inadequacy leads to severe combined immunodeficiency disease. Understanding the interaction of adenosine deaminase with inhibitors is crucial for the development of pharmaceutical agents. Computer simulations show these interactions. In the present study, the interactions between 6 inhibitors and adenosine deaminase were considered by binding free energy calculation. We used docking and molecular dynamic simulation methods to determine inhibitors binding free energy. In all casesthe 60 ns molecular dynamic simulations for free inhibitors and 60 ns molecular dynamics simulation for inhibitor-enzyme complex were performed. At the end, the inhibitors free energy of binding was calculated by using the linear interaction energy method. Our results clearly showed that non polar interactions play a significant role in determining the binding free energy. The results also demonstrated that the inhibitor binding site is a hydrophobic pocket that is completely surrounded by the hydrophobic residue. We also found that the stronger bindings lead to further reduction of solvent accessible surface area of the inhibitor in the inhibitor-enzyme complex. , it was also found that the inhibitor 6 (butyl 3-(6-amino-9H-purine-9-yl) propanoate have the lowest binding free energy and the maximum number of hydrogen bond between the inhibitor and adenosine deaminase, so that it makes greater interactions and can be used for more considerations and empirical studies.