An electronic effect on protein structure

The well‐known preference of the peptide bond for the trans conformation has been attributed to steric effects. Here, we show that a proline residue with an N‐formyl group (H_i−1−C′_i−1=O_i−1), in which H_i−1 presents less steric hindrance than does O_i−1, likewise prefers a trans conformation. Thus, the preference of the peptide bond for the trans conformation cannot be explained by steric effects alone. Rather, an n → π* interaction between the oxygen of the peptide bond (O_i−1), and the subsequent carbonyl carbon in the polypeptide chain (C′_i) also contributes to this preference. The O_i−1 and C′_i distance and O_i−1···C′_i=O_i angle are especially favorable for such an n → π* interaction in a polyproline II helix. We propose that this electronic effect provides substantial stabilization to this and other elements of protein structure.