Effects of side chains in helix nucleation differ from helix propagation

Stephen E. Miller, Andrew M. Watkins, Neville R. Kallenbach, Paramjit S. Arora

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Helix-coil transition theory connects observable properties of the α-helix to an ensemble of microstates and provides a foundation for analyzing secondary structure formation in proteins. Classical models account for cooperative helix formation in terms of an energetically demanding nucleation event (described by the σ constant) followed by a more facile propagation reaction, with corresponding s constants that are sequence dependent. Extensive studies of folding and unfolding in model peptides have led to the determination of the propagation constants for amino acids. However, the role of individual side chains in helix nucleation has not been separately accessible, so the σ constant is treated as independent of sequence. We describe here a synthetic model that allows the assessment of the role of individual amino acids in helix nucleation. Studies with this model lead to the surprising conclusion that widely accepted scales of helical propensity are not predictive of helix nucleation. Residues known to be helix stabilizers or breakers in propagation have only a tenuous relationship to residues that favor or disfavor helix nucleation.

Original languageEnglish
Pages (from-to)6636-6641
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number18
DOIs
StatePublished - 6 May 2014
Externally publishedYes

Keywords

  • Helix propensity
  • Synthetic helices

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