Extensive conformational searches of 13 representative dipeptides and an efficient method for dipeptide structure determinations based on amino acid conformers.

Conformations of peptides are the basis for their property studies and the predictions of peptide structures are highly important in life science but very complex in practice. Here, thorough searches on the potential energy surfaces of 13 representative dipeptides by considering all possible combinations of the bond rotational degrees of freedom are performed using the density functional theory based methods. Careful analyses of the conformers of the 13 dipeptides and the corresponding amino acids reveal the connections between the structures of dipeptide and amino acids. A method for finding all important dipeptide conformers by optimizing a small number of trial structures generated by suitable superposition of the parent amino acid conformations is thus proposed. Applying the method to another eight dipeptides carefully examined by others shows that the new approach is both highly efficient and reliable by providing the most complete ensembles of dipeptide conformers and much improved agreements between the theoretical and experimental IR spectra. The method opens the door for the determination of the stable structures of all dipeptides with a manageable amount of effort. Preliminary result on the applicability of the method to the tripeptide structure determination is also presented. The results are the first step towards proving Anfinsen's hypothesis by revealing the relationships between the structures of the simplest peptide and its constituting amino acids. It implies that the structures of peptides are not only determined by their amino acid sequences, but also closely linked with the amino acid conformations. Copyright 2009 Wiley Periodicals, Inc.