Answer these questions on the whiteboard (or paper). You may work in a group of 2 or 3. Be sure to verify your solution with a TA/instructor before leaving.
Basic (✓):
Construct a thermodynamic cycle for the $\Delta G$ of folding and mutating an amino acid residue of a protein (i.e., you have the transition going from unfolded to folded and the transition going from wild type to point mutant).
Write the formula for the $\Delta\Delta G$ of folding free energy due to a mutation.
Pretend that the only thing that matters is the configurational entropy. The table below provides per-residue $\Delta S$ values:
- $\Delta S_{bu\to ex}$: the entropy change associated with the transfer of a side chain that is buried in the interior of the protein to its surface
- $\Delta S_{ex\to u}$: the entropy change from a surface exposed side chain transitioning from a folded protein to an unfolded protein
- $\Delta S_{bb}$: the entropy change of the backbone when transitioning from a folded protein to an unfolded protein
That is, the $\Delta S$ of unfolding for a buried residue is $\Delta S = \Delta S_{bu\to ex} + \Delta S_{ex\to u} + \Delta S_{bb}$.
| Amino acid | $\Delta S_{bu\to ex}$ (cal/K·mol) | $\Delta S_{ex\to u}$ (cal/K·mol) | $\Delta S_{bb}$ (cal/K·mol) |
|---|---|---|---|
| ALA | 0.00 | 0.00 | 4.1 |
| ARG | 7.11 | −0.84 | 3.4 |
| ASN | 3.29 | 2.24 | 3.4 |
| ASP | 2.00 | 2.16 | 3.4 |
| CYS | 3.55 | 0.61 | 3.4 |
| GLN | 5.02 | 2.12 | 3.4 |
| GLU | 3.53 | 2.27 | 3.4 |
| GLY | 0.00 | 0.00 | 6.5 |
| HIS | 3.44 | 0.79 | 3.4 |
| ILE | 1.74 | 0.67 | 2.18 |
| LEU | 1.63 | 0.25 | 3.4 |
| LYS | 5.86 | 1.02 | 3.4 |
| MET | 4.55 | 0.58 | 3.4 |
| PHE | 1.40 | 2.89 | 3.4 |
| SER | 3.68 | 0.55 | 3.4 |
| THR | 3.31 | 0.48 | 3.4 |
| TRP | 2.74 | 1.15 | 3.4 |
| TYR | 2.78 | 3.12 | 3.4 |
| VAL | 0.12 | 1.29 | 2.18 |
Source: D'aquino JA, Gómez J, Hilser VJ, Lee KH, Amzel LM, Freire E. The magnitude of the backbone conformational entropy change in protein folding. Proteins: Structure, Function, and Bioinformatics. 1996 Jun;25(2):143-56.
Compute the $\Delta\Delta S$ of
- buried TRP to buried PHE
- buried ILE to buried VAL
- surface ARG to surface ALA
- buried ARG to surface GLY
Upload your solution to GradeScope.
Extra (✓+):
Work through the Colab notebook.
Upload your results to GradeScope.