College of Liberal Arts & Social Sciences Theses and Dissertations

Graduation Date

8-2010

Document Type

Thesis

Department/Program Conferring Degree

Physics

Keywords

Protein Denaturation, cold denaturation, small angle x-ray scattering, saxs, cytochrome C

Abstract

We present the first comprehensive study of the cold denaturation of proteins using Small Angle X‐Ray Scattering. The radius of gyration of equine Cytochrome‐C is determined for varying salt and denaturant conditions at temperatures ranging from ‐25 to 60 degrees Celsius. Radius of gyration measurements are then compared to a theoretical protein folding theory using by using a two‐state population model to relate thermodynamic quantities to physical measurements. The incorporation of a temperature‐dependent pH and solvent dielectric constant is critical to incorporating the electrostatic interactions of both the protein and the solution over this broad temperature range and properly predict the observed protein stability from sequence. At suitable conditions, the protein can be made to increase in size by nearly 9 Angstroms (over 60% of its native radius of gyration) when dropped in temperature from 0 to ‐25 degrees Celsius. This result is promising for future studies of ultrafast protein folding using time‐resolved SAXS where initially cold denatured protein will be suddenly jumped in temperature by an infrared laser to initiate folding. Further, this work validates modifications made to existing protein folding theory.

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