The effects of regularly spaced glutamine substitutions on alpha-helical peptide structures: A DFT/ONIOM study

The side-chains of the residues of glutamine (Q) and asparagine (N) contain amide groups. These can H-bond to each other in patterns similar to those of the backbone amides in α-helices. We show that mutating multiple Q’s for alanines (A’s) in a polyalanine helix stabilizes the helical structure, while similar mutations with multiple N’s do not. We suggest that modification of peptides by incorporating Q’s in such positions can make more robust helices that can be used to test the effects of secondary structures in biochemical experiments linked to proteins with variable structures such as tau and α-synuclein.