title: Molecular dynamics simulations of angiotensin II in aqueous and dimethyl sulfoxide environments.
abstract: Angiotensin II (Ang II) is an octapeptidic hormone, which plays an important role in the mechanisms of blood pressure control. In this work, extensive molecular dynamics (MD) simulations have been carried out on this peptide, both in aqueous and in dimethyl sulfoxide (DMSO) environments. Experimentally proposed models for the structure of angiotensin II in both environments are not consensual and the results obtained have provided some further insight about the structural properties of this hormone. In these simulations, the N-terminus of Ang II in the aqueous environment has been associated with a considerable larger flexibility than the correspondent C-terminus, but this was not found in the case of the DMSO environment. This is consistent with the assumption that the biological activity of Ang II is associated with its C-terminal residues embedded in a hydrophobic environment of its AT1 receptor. Other features detected in DMSO environment were an H(His6 imidazole)-O(Phe8 carboxylate) hydrogen bond and a salt-bridge structure involving the Asp1 and Arg2 side chains. An additional important conformational feature is the spatial proximity between Tyr4 and His6 in both water and DMSO environments. This molecular feature may trigger the interest for the synthetic chemists to apply rational design for the synthesis of novel AT1 antagonists.
authors.affiliation: REQUIMTE, Departamento de Química, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, 687, 4169-007 Porto, Portugal.
authors.forename: Marco A C
authors.initials: MA
authors.lastname: Preto
authors.forename: André
authors.initials: A
authors.lastname: Melo
authors.forename: Hernâni L S
authors.initials: HL
authors.lastname: Maia
authors.forename: Thomas
authors.initials: T
authors.lastname: Mavromoustakos
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Ramos
mesh_terms: D000804:Angiotensin II / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003198:Computer Simulation; D004121:Dimethyl Sulfoxide / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D012996:Solutions; D012997:Solvents; D014867:Water / Q000737:chemistry
chemical_list: D012996:Solutions; D012997:Solvents; D014867:Water; D000804:Angiotensin II; D004121:Dimethyl Sulfoxide