Molecular Dynamics Simulations of Small Peptides: Can One Derive Conformational Preferences from ROESY Spectra?

Christine Peter, Magnus Rueping, Hans Jakob Wörner, Bernhard Jaun, Dieter Seebach, Wilfred F. Van Gunsteren*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


Folding properties of β-peptides were investigated by means of NMR experiments and MD simulations of β-dipeptides, which serve as small test systems to study the influence of stereocenters and side chains on hydrogen-bond and consequently on secondary-structure formation. Two stereoisomers, SR and SS, of a Val-Phe dipeptide, and of the corresponding Ala-Ala dipeptide, and a Gly-Gly dipeptide were simulated in methanol for 40 ns. In agreement with experiment, the isomers of the Val-Phe dipeptide adopt quite different conformers at 298 K, the differences being reduced at 340 K. Interestingly, the SR isomer shows enhanced hydrogen bonding at the higher temperature. The adopted conformations are primarily determined by the R or S side chain substitution, and less by the type of side chain. Back-calculation of 1H ROESY spectra and 3J coupling constants from the MD simulations and comparison with the experimental data for the Val-Phe dipeptides shows good agreement between simulation and experiment, and reveals possible problems and pitfalls, when deriving structural properties of a small and extremely flexible molecule from NMR data only. Inclusion of all aspects of internal dynamics is essential to the correct prediction of the NMR spectra of these small molecules. Cross comparison of calculated with experimental spectra for both isomers shows that only a few out of many ROESY peaks reflect the sizeable conformational differences between the isomers at 298 K.

Original languageEnglish (US)
Pages (from-to)5838-5849
Number of pages12
JournalChemistry - A European Journal
Issue number23
StatePublished - Dec 5 2003
Externally publishedYes


  • Conformation analysis
  • Molecular dynamics
  • NMR spectroscopy
  • Peptides
  • β-peptides

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry


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