Protein recognition motifs: Design of peptidomimetics of helix surfaces

Ye Che, Bernard R. Brooks, Garland R. Marshall

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Helices represent one of the most common recognition motifs in proteins. The design of nonpeptidic scaffolds, such as the 3,2′,2″-tris- substituted terphenyl, that can imitate the side-chain orientation along one face of an α-helix potentially provides an effective means to modulate helix-recognition functions. Here, based on theoretical arguments, we described novel α-helix mimetics which are more effective than the terphenyl at constraining the aryl-aryl torsion angles to those associated with structures suitable for mimicking the α-helical twist for side-chain orientation and for superimposing the side chains of residues i, i + 3 or i + 4, i + 7 when compared with the α-β side-chain vectors of the regular α-helix with an improved root mean square deviation (RMSD) of approximately 0.5 Å. In addition, this study suggests that rotamer distributions around the Cα-Cβ bonds of these helix mimetics are similar to those of α-helices, except that these rotamer distributions show an approximately 60° shift compared to those of α-helices when the mimetic axis is superimposed upon the helix axis. This change in rotamer orientation complicates mimicry of the helix surface.

Original languageEnglish
Pages (from-to)288-297
Number of pages10
JournalBiopolymers
Volume86
Issue number4
DOIs
StatePublished - Jul 1 2007

Keywords

  • Conformational analysis
  • Peptidomimetic
  • Privileged structure
  • Side-chain
  • Template design
  • α-helix

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