title: Exploring the effect of side-chain substitutions upon the secondary structure preferences of β-peptides.
abstract: The ability to design well-folding β-peptides with a specific biological activity requires detailed insight into the relationship between the β-amino acid sequence and the dominant three-dimensional structure of such a peptide. To this end, secondary structure preferences of two sets of 16 β-peptides were investigated by means of one-step perturbation using molecular dynamics (MD) simulations. For each set of peptides, two reference-state simulations and one perturbed-state simulation were carried out to predict the secondary structure preferences for the other 15 peptides. The results show that the substitution of a methyl group in the third or fourth residue stabilizes the left-handed 3(14)-helix over the right-handed 2.7(10/12)-helix for the set of hexapeptides A; for the set of heptapeptides B, having methyl substitutions at both β- and α-carbon positions of the fourth or fifth residue stabilizes the left-handed 3(14)-helix over the right-handed 2.5(12)-helix. Not only the side-chain substitution pattern but also the side-chain composition affects the relative stability of different secondary structures. The approach described here may be of use in peptide design with an eye to obtaining peptides with particular folds and biological activities.
authors.affiliation: Laboratory of Physical Chemistry, Swiss Federal Institute of Technology, ETH, Zürich, Switzerland.
authors.forename: Zhixiong
authors.initials: Z
authors.lastname: Lin
authors.forename: Wilfred F
authors.initials: WF
authors.lastname: van Gunsteren
mesh_terms: D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D009842:Oligopeptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013816:Thermodynamics
chemical_list: D009842:Oligopeptides