Chapter 6, Problem 23P

Disulfide bonds have been shown to stabilize proteins (i.e., make them less likely to unfold). Consider the cases shown schematically below for two variants of the same protein. In case #1 the disulfide forms between Cys residues that have been introduced near the protein N- and C-termini, and in case #2 the disulfide forms between Cys residues that have been introduced in the middle of the protein sequence. Which protein is likely to be more stable? (Note: Assume the disulfide bond is intact in both the unfolded and folded states). Explain your reasoning.