Structural insight on the activity of type 1 angiotensin II peptide antagonists using MD simulations

Angiotensin II (AngII) is an octapeptide hormone, which plays a very important role in the blood pressure control mechanism. The excess production of this hormone is one of the main causes of hypertension illness. The antagonists for AngII At1 receptor constitute some of the most effective antihypertension drugs. In this work, both tested type1 AngII antagonists as well as new modeled antagonists (obtained by substitution of nonspecific amino acids by noncode residues (Sarcosine (Sar) and several Calpha, Calpha-dialkylglycines)) were simulated in dimethyl sulfoxide (DMSO) using molecular dynamics (MD). A number of common structural characteristics were identified on the active (and potentially active) simulated analogs, which seem to be correlated with their antagonistic activity. Two of the designed analogs were proposed as possible antagonists.