A short-hand calculation for estimating energetics in kcal/mol is:
∆G=1.4pK
where pK=-logK
The peptide bond has a partial double-bond character between the C–N with a barrier to rotation of 20 kcal/mol, which makes it very unfavorable to rotate along the peptide bond. The trans orientation is most favored to minimize steric clash between amino acid R groups. In small molecule models (e.g. N-methylacetamide), the free energy change for trans to cis isomerization is 2.6 kcal/mol. What percent of cis amide bonds would be expected?
In proteins, trans peptide bonds are observed 1000 to 1 in comparison to cis peptide bonds. What free energy change would correspond to this ratio of cis:trans peptides?
When the i+1 residue in a peptide is a proline, the free energy change for the cis:trans isomerization is 0.5 kcal/mol. How does the expected percentage of cis peptides at these proline sites compare to what is observed (~6.5%).
Summarize and connect the findings of parts a-c of this question. Where do you predict cis peptide bonds to be located relative to a protein structure?