Structure and reorientational dynamics of angiotensin I and II: a microscopic physical insight

• Published in: Journal of biomolecular structure & dynamics 2012, Vol.29 (6), p.1175-1194
• Main Authors: DeLeon, Kristi Y., Patel, Achal P., Kuczera, Krzysztof, Johnson, Carey K., Jas, Gouri S.
• Format: Article
• Language: English
• Subjects: Angiotensin; Angiotensin I - chemistry; Angiotensin I - metabolism; Angiotensin II - chemistry; Angiotensin II - metabolism; anisotropy decay; Circular Dichroism; Fluorescence Polarization; FTIR; molecular dynamics; Molecular Dynamics Simulation; Peptides - chemistry; Peptides - metabolism; Protein Conformation; reorientational dynamics; Spectroscopy, Fourier Transform Infrared; Structure-Activity Relationship; Water - chemistry
• ISSN: 0739-1102; 1538-0254
• DOI: 10.1080/07391102.2011.672631

We present a study of structural analysis and reorientational dynamics of Angiotensin I (AngI) and Angiotensin II (AngII) in aqueous solution. AngI is a decapeptide that acts as a precursor to the octapeptide AngII in the Renin-Angiotensin-Aldosterone system for blood pressure regulation. Experimental structural characterization of these peptides, carried out with circular dichroism and infrared spectroscopy, showed that the angiotensins are mostly disordered but exhibit a measurable population of ordered structures at room temperature. Interestingly, these change from the unordered polyproline-like conformation for AngI to a more compact and ordered conformation for AngII as the length of the peptide is decreased. Anisotropy decay measurements with picosecond time resolution indicate slower overall tumbling and a greater amplitude of internal motion in AngI compared to AngII, consistent with more compact and less flexible structure of the active form of the peptide. To model the microscopic behavior of the peptides, 2-μs molecular dynamics simulation trajectories were generated for AngI and AngII, at 300 K using the OPLS-AA potential and SPC water. The structures sampled in the simulations mostly agree with the experimental results, showing the prevalence of disordered structures, turns, and polyproline helices. Additionally, the computational results predict fewer sampled conformations, tighter side-chain packing and marked increase of Phe8 solvent accessibility upon AngI truncation to AngII. Our combined approach of experiment and extensive computer simulation thus yields new information on the conformational dynamics of the angiotensins, helping provide insight into the structural basis for the potency of AngI relative to AngII.