Quantitative description of residual helical structure for λ-repressor N-terminal domain in the unfolded state

Proteins can form residual compactness in the unfolded state. Among different types of residual compactness, residual helical structure is an important type of local compactness that can propagate through the formation of helical hydrogen bonds. Residual helicity has been observed for different unfolded state proteins. In order to accurately determine the contributions of individual residues to the overall helicity, accurate determination of residue-specific information and quantitative analysis methods are needed.

The projects in this dissertation aim at quantitatively describing the residual helical conformation in the unfolded state of λ-repressor N-terminal domain. The residue-specific helicity values and backbone amide proton hydrogen bonding populations are analyzed using improved methods based on Bayesian inference. Generally, these values are higher for the helix 1 region in the context of the N-terminal domain than as an isolated peptide. Experimentally determined residue-specific helicity values of unfolded state λ-repressor N-terminal domain show similarity to the theoretical prediction using helix-coil model.

These results show that, in the unfolded state of λ-repressor N-terminal domain, the propagation of residual helicity does not significantly depend on tertiary interactions. The results support the hypothesis that λ-repressor N-terminal domain folds by “diffusion-collision”.