European Biophysics Journal

, Volume 32, Issue 8, pp 661–670

Circular dichroism spectra of β-peptides: sensitivity to molecular structure and effects of motional averaging

  • Xavier Daura
  • Dirk Bakowies
  • Dieter Seebach
  • Jörg Fleischhauer
  • Wilfred F. van Gunsteren
  • Peter Krüger
Article

Abstract

Circular dichroism spectra of two β-peptides, i.e. peptides composed of β-amino acids, calculated using ensembles of configurations obtained by molecular dynamics simulation are presented. The calculations were based on 200 ns simulations of a β-heptapeptide in methanol at 298 K and 340 K and a 50 ns simulation of a β-hexapeptide in methanol at 340 K. In the simulations the peptides sampled both folded (helical) and unfolded structures. Trajectory structures with common backbone conformations were identified and grouped into clusters. The CD spectra were calculated for individual structures, based on peptide-group dipole transition moments obtained from semi-empirical molecular orbital theory and using the so-called matrix method. The single-structure spectra were then averaged over entire trajectories and over clusters of structures. Although certain features of the experimental CD spectra of the β-peptides are reproduced by the trajectory-average spectra, there exist clear differences between the two sets of spectra in both wavelength and peak intensities. The analysis of individual contributions to the average spectra shows that, in general, the interpretation of a CD signal in terms of a single structure is not possible. Moreover, there is a large variation in the CD spectra calculated for a set of individual structures that belong to the same cluster, even when a structurally tight clustering criterion is used. This indicates that the CD spectra of these peptides are very sensitive to small local structural differences.

Keywords

Circular dichroism Cluster analysis Computer simulation Molecular dynamics Peptide folding 

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Copyright information

© EBSA 2003

Authors and Affiliations

  • Xavier Daura
    • 1
    • 4
  • Dirk Bakowies
    • 1
  • Dieter Seebach
    • 2
  • Jörg Fleischhauer
    • 3
  • Wilfred F. van Gunsteren
    • 1
  • Peter Krüger
    • 1
    • 3
  1. 1.Laboratory of Physical ChemistrySwiss Federal Institute of Technology ZurichZurichSwitzerland
  2. 2.Laboratory of Organic ChemistrySwiss Federal Institute of Technology ZurichZurichSwitzerland
  3. 3.Institut für Organische ChemieRWTH AachenAachenGermany
  4. 4.Institució Catalana de Recerca i Estudis Avançats (ICREA) and Institute of Biotechnology and BiomedicineUniversitat Autònoma de BarcelonaBellaterraSpain

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