Using Heat Effects on Coil Hydrodynamic Size to Reveal the Nature and Energetics of Denatured State Conformational Bias
| dc.contributor.advisor | Whitten, Steven T. | |
| dc.contributor.author | Paiz, Elisia | |
| dc.contributor.committeeMember | Lewis, Karen A. | |
| dc.contributor.committeeMember | Kerwin, Sean M. | |
| dc.date.accessioned | 2021-03-29T14:11:14Z | |
| dc.date.available | 2021-03-29T14:11:14Z | |
| dc.date.issued | 2019-12 | |
| dc.description.abstract | Conformational equilibria in the protein denatured state have key roles regulating folding, stability, and function. The extent of conformational bias in the denatured state under folding conditions, however, has thus far proven elusive to quantify, particularly with regard to its sequence dependence and energetic character. To better understand the structural preferences of the denatured state, we analyzed both the sequence dependence to the mean hydrodynamic size of intrinsically disordered proteins (IDPs) and the impact of heat on the coil dimensions, demonstrating that the sequence dependence and thermodynamic energies associated with intrinsic biases for the α and polyproline II (PPII) backbone conformations can be obtained. This result was determined by using a model of the denatured state whereby the position-specific conformational preferences of IDPs were very locally determined. To test these results, two sets of experiments were performed. First, experiments were designed to determine if this method for measuring conformational bias is limited to IDP sequences, which are known to be depleted, relative to foldable protein sequences, in hydrophobic content. By designing unfolded mutant proteins from foldable sequences, it was shown that hydrophobic-rich sequences likewise experience hydrodynamic size changes that relate to heat effects on backbone structure. Second, we designed experiments to test whether the structural features we observe are indeed locally determined. By scrambling the mutant sequences multiple times, it was determined that the structural features of these proteins were, surprisingly, independent of the arrangement | |
| dc.description.department | Chemistry and Biochemistry | |
| dc.format | Text | |
| dc.format.extent | 100 pages | |
| dc.format.medium | 1 file (.pdf) | |
| dc.identifier.citation | Paiz, E. A. (2019). <i>Using heat effects on coil hydrodynamic size to reveal the nature and energetics of denatured state conformational bias</i> (Unpublished thesis). Texas State University, San Marcos, Texas. | |
| dc.identifier.uri | https://hdl.handle.net/10877/13297 | |
| dc.language.iso | en | |
| dc.subject | Protein denatured state | |
| dc.subject | Intrinsic conformational propensities | |
| dc.subject | Hydrodynamic size | |
| dc.subject | Biophysics | |
| dc.title | Using Heat Effects on Coil Hydrodynamic Size to Reveal the Nature and Energetics of Denatured State Conformational Bias | |
| dc.type | Thesis | |
| thesis.degree.department | Chemistry and Biochemistry | |
| thesis.degree.discipline | Biochemistry | |
| thesis.degree.grantor | Texas State University | |
| thesis.degree.level | Masters | |
| thesis.degree.name | Master of Science |