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Structure, dynamics, and interactions of Angiotensin family of peptides with functional implications.

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dc.contributor.advisor Jas, Gouri Sankar.
dc.contributor.author DeLeon, Kristine Y.
dc.date.copyright 2011-12
dc.identifier.uri http://hdl.handle.net/2104/8257
dc.description.abstract We present a study of structural analysis and reorientational dynamics of the angiotensin family of peptides. AngI is a decapeptide that acts as a precursor to the octapeptide, AngII in the Renin Angiotensin Aldosterone system for blood pressure regulation. Smaller metabolites of AngII, including AngIII, AngIV and Ang₁₋₇, have recently been discovered to play an important role in 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 polyproline helix for AngI to the left-handed helical conformation for AngII, III, and IV. Additionally, the antagonist, Ang₁₋₇, was found to contain a significant population of right handed α-helix. Anisotropy decay measurements with picosecond time resolution indicates a slower overall tumbling and a greater amplitude of internal motion in AngI and Ang₁₋₇ compared to AngII, which is consistent with a more compact and less flexible structure in AngII. 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. The main difference is the lack of significant presence of left-handed helices in the trajectories. 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. en_US
dc.publisher en
dc.rights Baylor University theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. Contact librarywebmaster@baylor.edu for inquiries about permission. en_US
dc.subject Renin-angiotensin system. en_US
dc.title Structure, dynamics, and interactions of Angiotensin family of peptides with functional implications. en_US
dc.type Thesis en_US
dc.description.degree Ph.D. en_US
dc.rights.accessrights No access - Contact librarywebmaster@baylor.edu en_US
dc.contributor.department Biomedical Studies. en_US
dc.contributor.schools Baylor University. Institute of Biomedical Studies. en_US


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