title: Can one derive the conformational preference of a beta-peptide from its CD spectrum?
abstract: CD spectroscopy is often used to elucidate the secondary structure of peptides built from non-natural amino acids such as beta-amino acids. The interpretation of such CD spectra is not always unambiguous. Here, we present a case where two beta-hexapeptides, a dimethyl-beta-hexapeptide indicated as DM-BHP (A) and its nonmethylated analogue indicated as BHP (B), exhibit similar CD spectra, whereas they are expected to differ in secondary structure. The structural properties of both peptides were studied by molecular dynamics simulation, and from the resulting trajectories, the corresponding CD spectra were calculated. Starting from a fully extended conformation, BHP is observed to form a 3(14)-helix, while DM-BHP remains unfolded. However, even though these two peptides hardly share any conformations, their calculated CD spectra are alike and show the same features as the experimentally measured ones. Our results imply that a particular CD pattern can be induced by spatially different structures, which makes it difficult to derive the conformational preference of a peptide from its CD spectrum alone. To gain more insight into the relationship between the preferred conformation of a peptide and its CD spectrum, more accurate methods to calculate the CD spectrum for a given conformation are required.
authors.affiliation: Laboratory of Physical Chemistry, Swiss Federal Institute of Technology Zürich, ETH-Hönggerberg, CH-8093 Zürich, Switzerland.
authors.forename: Alice
authors.initials: A
authors.lastname: Glättli
authors.forename: Xavier
authors.initials: X
authors.lastname: Daura
authors.forename: Dieter
authors.initials: D
authors.lastname: Seebach
authors.forename: Wilfred F
authors.initials: WF
authors.lastname: van Gunsteren
mesh_terms: D002942:Circular Dichroism / Q000379:methods*; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary
chemical_list: D009842:Oligopeptides