Secondary Structure of Ac-Alan-LysH+ Polyalanine Peptides (n=5, 10, 15) in Vacuo: Helical or Not?

The polyalanine-based peptide series Ac-Ala(n)-LysH(+) (n = 5-20) is a prime example that a secondary structure motif that is well-known from the solution phase (here: helices) can be formed in vacuo. Here we revisit the series members n = 5,10,15, using density functional theory (van der Waals corrected generalized gradient approximation) for structure predictions, which are then corroborated by room temperature gas-phase infrared vibrational spectroscopy. We employ a quantitative comparison based on Pendry's reliability factor (popular in surface crystallography). In particular, including anharmonic effects into calculated spectra by way of ab initio molecular dynamics produces remarkably good experiment-theory agreement. We find the longer molecules (n = 10,15) to be firmly alpha-helical in character. For n = 5, calculated free-energy differences show different H-bond networks to still compete closely. Vibrational spectroscopy indicates a predominance of alpha-helical motifs at 300 K, but the lowest-energy conformer is not a simple helix.