Angular variances for internal bond rotations of side chains in GXG- based tripeptides derived from 13C-nmr relaxation measurements: Implications to protein folding

Dmitri V. Mikhailov, Lais Washington, Alexei M. Voloshin, Vladimir A. Daragan, Kevin H. Mayo

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


The study of backbone and side-chain internal motions in proteins and peptides is crucial to having a better understanding of protein/peptide 'structure' and to characterizing unfolded and partially folded states of proteins and peptides. To achieve this, however, requires establishing a baseline for internal motions and motional restrictions for all residues in the fully, solvent-exposed 'unfolded state.' GXG-based tripeprides are the simpliest peptides where residue X is fully solvent exposed in the context of an actual peptide. In this study, a series of GXG-based tripeptides has been synthesized with X being varied to include all twenty common amino acid residues. Proton-coupled and -decoupled 13C-nmr relaxation measurements have been performed on these twenty tripeprides and various motional models (Lipari-Szabo model free approach, rotational anisotropic diffusion, rotational fluctuations within a potential well, rotational jump model) have been used to analyze relaxation data for derivation of angular variances and motional correlation times for backbone and side-chain χ1 and χ2 bonds and methyl group rotations. At 298 K, backbone motional correlation times range from about 50 to 85 ps, whereas side-chain motional correlation times show a much broader spread from about 18 to 80 ps. Angular variances for backbone φ,ψ bond rotations range from 11°to 23°and those for side chains vary from 5°to 24°for χ1 bond rotations and from 5°to 27°for χ2 bond rotations. Even in these peptide models of the 'unfolded state,' side-chain angular variances can be as restricted as those for backbone and β-branched (valine, threonine, and isoleucine) and aromatic side chains display the most restricted motions probably due to steric hinderence with backbone atoms. Comparison with motional data on residues in partially folded, β-sheet-forming peptides indicates that side-chain motions of at least hydrophobic residues are less restricted in the partially folded state, suggesting that an increase in side-chain conformational entropy may help drive early-stage protein folding.

Original languageEnglish (US)
Pages (from-to)373-383
Number of pages11
Issue number5
StatePublished - Apr 15 1999


  • C-nmr measurements
  • Angular variances
  • GXG-based tripeptides
  • Internal bond rotations
  • Protein folding
  • Side chains

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