Amino acids with hydrogen-bonding side chains have an intrinsic tendency to sample various turn conformations in aqueous solution.

Local structure in unfolded proteins, especially turn segments, has been suggested to initiate the hierarchical protein-folding process. To determine the intrinsic propensity to form such turn structures, amide I' band profiles of the Raman, IR, and vibrational circular dichroism (VCD) spectra, and several structure-sensitive NMR J-coupling constants, have been measured for a series of GxG (x=D, N, T, C) peptides, in which the central x residues are abundant in various turn motifs in folded proteins. In addition, we revisited earlier measured GSG experimental data. To check whether this relatively high propensity for these residues to sample turns reflects an intrinsic propensity, the experimental data were analyzed in terms of conformational distributions that can be described as a superposition of two-dimensional Gaussian distributions associated with different so-called mesostates. The analysis reveals that the investigated residues sample dihedral angles similar to those found in the corner residues of various turns, namely, type I/I', II/II', and IV β-turns. Aspartic acid (D) was found to predominantly sample regions attributed to turns, including distributions at the upper border of the upper-right quadrant of the Ramachandran plot, which bear some resemblance to asx-turns observed in proteins. This conformation enables hydrogen bonding between the side-chain carboxylate and the C-terminal amide group. Altogether, the study shows that the high propensity for T, S, C, N, and D to be located in turn motifs reflects, to a substantial degree, an intrinsic property and supports the role of these residues as initiation sites for hierarchical folding processes that can lead to compact structures in the unfolded state of peptides and proteins.