Question

Do you expect a Pro→Gly mutation in a surface-loop region of a globular protein to be stabilizing or destabilizing? Assume the mutant folds to a native-like conformation. Explain your answer in terms of the predicted enthalpic and entropic effects of the mutation on the ΔG for protein folding compared to ΔG of folding for the wild-type protein.

Match the items in the left column to the appropriate blanks in the sentences on the right.

ASsolvent Because the mutation is on the surface, loss of contacts in the similar protein core is and the amino acid is likely to be interacting with solvent to extents in both folded and unfolded states; thus, effects stabilizing are predicted to be minimal. on a big issue destabilize The is likely to be small because side-chain solvation is predicted to in both the folded and unfolded states. changes be stabilization the most due to the conformational flexibility of Gly compared to Pro Cunfolding (wt) Gly will both the folded and the unfolded states; however, it will destabilization the unfolded state more due to the dramatic increase in destabilizing conformational entropy of the unfolded state as a result of this mutation. stabilize The of the unfolded state for the mutant means that not an issue is greater than ; thus, the mutation is Δ unfolding (mutant) hydrophilic different hydrophobic protein

Answer 1

1. Hydrophilic

2. Destabilizing

3. Similar

4. Stabilizing

5. S solvent

6. Different

7. Destabilize

8. Stabilize

9. H

10. Destabilization

11. G unfolded (mutant)

12. G unfolded (w)

13. G unfolded (w)

14. Destabilizing