Rotamer Libraries for the High-Resolution Design of β-Amino Acid Foldamers

Andrew M. Watkins, Timothy W. Craven, P. Douglas Renfrew, Paramjit S. Arora, Richard Bonneau

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1771-1780.e3
JournalStructure
Volume25
Issue number11
DOIs
StatePublished - Nov 7 2017

Keywords

  • computational biology
  • design
  • peptides
  • peptidomimetics
  • proteins
  • rotamers
  • structural bioinformatics

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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