Angiotensin converting enzyme (ACE) plays an important role in blood pressure control systems (renin-angiotensin system) because it converts angiotensin I to angiotensin II (Ang II), which leads to the development of hypertension. Therefore, it is very important to study ACE inhibition for the prevention and treatment of hypertension. ACE inhibitors are widely prescribed for cardiovascular diseases, including high blood pressure, heart failure, and kidney failure. ACE inhibiting peptides are safer than synthetic ACE inhibitors and may be useful as antihypertensive agents. In this work, the spatial structure and conformational behavior of the antihypertensive tripeptide İRW and its isomer LRW, isolated from food proteins, have been studied using molecular mechanics methods. As a result of calculations, it was shown that, in a weakly polar environment, peptides preferentially form similar stable fully folded structures. It was shown that the preferred conformation of these peptides is stabilized by effective dispersion interactions with the formation of a hydrogen bond between the atoms of the carboxyl group of the C-terminal part and the guanidine group of the arginine side chain. As a result of a comparative study of two structurally homologous tripeptides IRW and LRW, the energetically preferred ranges of the dihedral angles and the mutual arrangement of residues in the low-energy conformations of molecules were determined. Based on the obtained parameters, molecular models of the energetically preferred conformations of the tripeptides were compiled. This study made it possible to compare all the stable conformational states of two tripeptide peptides, which makes it possible to identify structural criteria that may be necessary to create inhibitory properties of drugs for clinical use.
antihypertensive tripeptide, angiotensin converting enzyme (ACE), conformation, inhibitor, molecular mechanics method
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