CONFORMATIONAL STUDY OF ANGIOTENSIN-II

Conformational free energy calculations using an empirical potential E CEPP/3 (Empirical Conformational Energy Program for Peptides, Version 3) were carried out on angiotensin II (AII) of sequence Asp-Arg-Val-Ty r-Ile-His-Pro-Phe to find the stable conformations of the free state i n the unhydrated and the hydrated states. A conformational analysis of the unhydrated state was carried out using the buildup procedure. The free energy calculation using the hydration shell model was also carr ied out to obtain the stable conformation of the hydrated state. The c alculated stable conformations of AII in both states have a partially right-handed alpha-helical structure stabilized by short- and medium-r ange interactions. The similarity between the lowest free energy confo rmations of the unhydrated and hydrated states suggests that the hydra tion might not be important to stabilize the overall conformation of A II in a free state. The absence of any intramolecular interaction of t he Tyr side chain suggests the possible interaction of this residue wi th the receptor. In this study, we found that the low free energy conf ormations contain both the parallel-plate and the perpendicular-plate geometries of the His and Phe rings, suggesting tile coexistence of bo th conformations. (C) 1996 John Wiley & Sons, Inc.