Optimizing the Fold Stability of Miniprotein Sequences

  • D. Victoria Williams
  • Jasper C. Lin
  • Brandon L. Kier
  • Niels H. Andersen
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (volume 611)


Peptides (< 25 residues) rarely have well-defined, deep energy wells for folding with the possible exception of a reported few hairpin and miniprotein structures. However, these systems display relatively low melting temperatures and broad thermal transitions for unfolding. Our lab has recently employed several strategies that provide exceptional stability for both types of folds.

In the case of the Trp-cage motif, combining helix stabilizing mutations with one other feature provided three mutants that display T M values greater than 75°C, with two-state folding (Fig. 1). In the β hairpin, Trp/Trp pairings flanking a turn have been shown to greatly stabilize folds [ 1]. These residue pairs adopt an edge-to-face (EtF) geometry, as evidenced by circular dichroism (CD) exciton couplets and an upfield Trp Hε3 proton (−2.2 ppm). Adding a backbone-NH/indole H-bonding interaction to a turn motif stabilized by an EtF Trp/Trp interaction, produced a 10-mer hairpin that is greater...


Circular Dichroism Cyclic Peptide Circular Dichroism Data Backbone Torsion Backbone Torsion Angle 
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The work was funded by an NIH grant (GM050658) to N. H. Andersen.


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • D. Victoria Williams
    • 1
  • Jasper C. Lin
    • 1
  • Brandon L. Kier
    • 1
  • Niels H. Andersen
    • 1
  1. 1.Department of ChemistryUniversity of WashingtonSeattle

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