Energetics and structure of alanine-rich α-helices via adaptive steered molecular dynamics

The energetics and hydrogen bonding profiles of the helix-to-coil transition were found to be an additive property and to increase linearly with chain length, respectively, in alanine-rich alpha-helical peptides. A model system of polyalanine repeats was used to establish this hypothesis for the energetic trends and hydrogen bonding profiles. Numerical measurements of a synthesized polypeptide Ac-Y(AEAAKA)(k)F-NH2 and a natural alpha-helical peptide a2N (1-17) provide evidence of the hypothesis's generality. Adaptive steered molecular dynamics was employed to investigate the mechanical unfolding of all of these alanine-rich polypeptides. We found that the helix-to-coil transition is primarily dependent on the breaking of the intramolecular backbone hydrogen bonds and independent of specific side-chain interactions and chain length. The mechanical unfolding of the alpha-helical peptides results in a turnover mechanism in which a 3(10)-helical structure forms during the unfolding, remaining at a near constant population and thereby maintaining additivity in the free energy. The intermediate partially unfolded structures exhibited polyproline II helical structure as previously seen by others. In summary, we found that the average force required to pull alanine-rich alpha-helical peptides in between the endpoints-namely the native structure and free coil-is nearly independent of the length or the specific primary structure.

Automated summary

The study found that the energetics and hydrogen bonding profiles of the helix-to-coil transition in alanine-rich alpha-helical peptides are additive properties and increase linearly with chain length. The mechanical unfolding of these peptides primarily relies on breaking intramolecular backbone hydrogen bonds and is independent of specific side-chain interactions and chain length. The average force required to pull these peptides between their native structure and a free coil is nearly independent of length or specific primary structure.