Figure 3. NMR structure of a bulge-like CDR-H3 β-hairpin mimic in aqueous solution.

(A) Backbone amide H_N and H_α chemical shift deviations (CSDs) for hairpin 1d highlighting a downfield abnormality at the bulge D15:Y16 residues. (B) Strip cross sections through the NOESY spectrum of hairpin 1d locating the A4:W17 and [R5,D15]:Y16 long-range correlations through space (left), along with the most significant side-chain CSD values for these residues. (C) Upfield CSDs recorded for the bulge residue 4 (A/V) reflecting a CH-π shielding interaction created by W17. (D) Overlay of ¹H NMR traces revealing the W17(H_ε1) signal line broadening with the temperature indicative of a weak intramolecular hydrogen-bond in 1d. (E) Dynamic structure of the bulged-like hairpin 1d in solution (PDB code: 8W0Q). Overlay of the five main conformer populations representative of the global 20-state ensemble of 1d elucidated by NMR spectroscopy and computational modeling with the stabilizing terminal β-strap (grey side chains) and the kinked/extended base of the β-bulge-like structure (magenta/blue).