Existence of Specific “Folds” in Polyproline II Ensembles of an “Unfolded” Alanine Peptide Detected by Molecular Dynamics

Equilibrium ensembles of octaalanine (Ac−Ala₈−NHMe) in water, prepared with MD, are analyzed for contributing microstates with an RMSD-based conformational clustering algorithm. The extracted ensemble-averaged properties are in excellent agreement with numerous spectroscopic measurements reported with small alanine model peptides in water. However, the dominantly polyproline II-like ensemble of the peptide is found to be populated with a handful of highly position-specific “folds”, including β-turns, β-hairpins, and helix nuclei, which could be the “seeds” that initiate proteins along their folding pathways.