Characterization of non-alpha helical conformations in Ala peptides

The folded (alpha helical) and unfolded (non-alpha helical) ensembles of the 21 amino acid peptide Ace-A21-Nme are characterized structurally. The replica exchange molecular dynamics approach is used to generate these ensembles at 46 different temperatures ranging from 278 to 487 K. Each replica system is simulated in explicit solvent for a period of 10 ns/replica, for a total of 460 ns. In addition to alpha helices, poly proline II (PPII) structures were identified to occur significantly. At low T the alpha helical content is larger than the PPII content, but near 300 K the PPII population is larger. Below 300 K, the PPII population increases with T, but it decreases above 300 K. The alpha helical content decreases with temperature. At temperatures below 300 K, there is a PPII propagation free energy that enhances the formation of long segments of PPII structure. This propagation term is smaller than for alpha helices. PPII segments of length 8 or less are more likely to form than alpha helices of the same length. The obtained low propensity for the formation of PPII segments of length shorter than five suggest that the interactions are responsible for the formation of PPII structures require a PPII segment of at least four amino acids. Stretches of four consecutive amino acids in the PPII conformations are needed for the formation of a groove around the peptide backbone that is strongly hydrated. Water in this groove is delocalized along a channel formed by the peptide in the PPII conformation.