Steric restrictions in protein folding: An α-helix cannot be followed by a contiguous β-strand

Nicholas C. Fitzkee, George D. Rose

Research output: Contribution to journalArticle


Using only hard-sphere repulsion, we investigated short polyalanyl chains for the presence of sterically imposed conformational constraints beyond the dipeptide level. We found that a central residue in a helical peptide cannot adopt dihedral angles from strand regions without encountering a steric collision. Consequently, an α-helical segment followed by a β-strand segment must be connected by an intervening linker. This restriction was validated both by simulations and by seeking violations within proteins of known structure. In fact, no violations were found within an extensive database of high-resolution X-ray structures. Nature's exclusion of α-β hybrid segments, fashioned from an α-helix adjoined to a β-strand, is built into proteins at the covalent level. This straightforward conformational constraint has far-reaching consequences in organizing unfolded proteins and limiting the number of possible protein domains.

Original languageEnglish (US)
Pages (from-to)633-639
Number of pages7
JournalProtein Science
Issue number3
StatePublished - Mar 2004


  • Protein folding
  • Protein secondary structure
  • Ramachandran plot
  • Unfolded protein

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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