Rotamer libraries for the high-resolution design of β-amino acid foldamers

β-amino acids offer attractive opportunities to develop biologically active peptidomimetics, either employed alone or in conjunction with natural α-amino acids. Owing to their potential for unique conformational preferences that deviate considerably from α-peptide geometries, β-amino acids greatly expand the possible chemistries and physical properties available to polyamide foldamers. Complete in silico support for designing new molecules incorporating nonnatural amino acids typically requires representing their side chain conformations as sets of discrete rotamers for model refinement and sequence optimization. Such rotamer libraries are key components of several state of the art design frameworks. Here we report the development, incorporation in to the Rosetta macromolecular modeling suite, and validation of rotamer libraries for β 3 -amino acids.