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 non-natural 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 β3-amino acids. Watkins et al. have constructed the first fully backbone-dependent rotamer libraries for β-amino acids; they agree well with higher levels of theory as well as experimental structures. These rotamer libraries permit them to be accurately modeled and designed using software such as Rosetta.
- computational biology
- structural bioinformatics