Molecular dynamics simulations of angiotensin II in aqueous and dimethyl sulfoxide environments

• Type: Article in International Scientific Journal
• Date: 2005

Authors

Preto, MAC (Author) Other; Melo, A (Author) FCUP; Maia, HLS (Author) Other; Mavromoustakos, T (Author) Other; Ramos, MJ (Author) FCUP

Journal

Title: Journal of Physical Chemistry B

Vol. 109

Pages: 17743-17751

ISSN: 1520-6106

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 20 Citations

Scopus - 19 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: P-000-1AR

DOI: 10.1021/jp0521048

Abstract (EN): 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 AspI 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 ATI antagonists.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9