Molecular Docking Analysis of Human Somatic and Testicular Angiotensin Converting Enzyme Complexed with a Novel Compound Gly-Val-Arg

Hypertension is one of the most common chronic diseases affecting millions of people worldwide. The structure-based drug design targeting domains of the ACE is important in the treatment of hypertension. The domain specificity inhibition of somatic ACE and testicular ACE by tripeptide GVR by binding to the specified active site of ACE has not been previously described. From this study, it was shown that tripeptide GVR was significantly bound to the active site of the C-domain of somatic ACE as compared to the N-domain Although tripeptide GVR was mimicking captopril, a strong inhibition of the C-domain's active site and a weak inhibition of the N-domain by GVR probably led to less significant side effects to the patients as compared to the strong non-domain specific inhibitor, captopril. Besides, the ability of tripeptide GVR to strongly inhibit testicular ACE was also shown. From this study, it has been shown that tripeptide GVR was able to bind on both somatic ACE and testicular ACE. It was also shown that the existence of arginine amino acid at the C-terminal of a peptide sequence was essential to inhibit ACE significantly.