Theoretical Studies on the Alanine-rich Peptide

The alanine-based peptide Ac-XX(A)₇OO-NH₂, referred to as XAO, where X, A, and O denote diaminobutyric acid, alanine, and ornithine, respectively, has recently been proposed to possess a well-defined polyproline II (P_II) conformation at low temperatures. The theoretical calculations, reported here present evidence that, on the contrary, this peptide does not have any significant amount of organized P_II structure, but exists in an ensemble of conformations with a distorted bend in the N-and C-termini regions. The conformational ensemble was obtained by molecular dynamics/simulated annealing calculations using the AMBER suite of programs with time-averaged distance and dihedral-angle restraints obtained from ROE volumes and vicinal coupling constants ³J_HNHα, respectively. The computed ensemble-averaged radius of gyration Rg (7.4 ± 1.0) Å is in excellent agreement with that measured by small angle X-ray scattering while, if the XAO peptide were in the Pn conformation, Rg would be 11.6 Å. The “P_II conformation” should be considered as one of the accessible conformational states of individual amino-acid residues in peptides and proteins rather than as a structure of most of the chain in the early stage of folding.