From coiled coils to small globular proteins: design of a native-like three-helix bundle

Protein Sci. 1998 Jun;7(6):1404-14. doi: 10.1002/pro.5560070617.


A monomolecular native-like three-helix bundle has been designed in an iterative process, beginning with a peptide that noncooperatively assembled into an antiparallel three-helix bundle. Three versions of the protein were designed in which specific interactions were incrementally added. The hydrodynamic and spectroscopic properties of the proteins were examined by size exclusion chromatography, sedimentation equilibrium, fluorescence spectroscopy, and NMR. The thermodynamics of folding were evaluated by monitoring the thermal and guanidine-induced unfolding transitions using far UV circular dichroism spectroscopy. The attainment of a unique, native-like state was achieved through the introduction of: (1) helix capping interactions; (2) electrostatic interactions between partially exposed charged residues; (3) a diverse collection of apolar side chains within the hydrophobic core.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Chemical Phenomena
  • Chemistry, Physical
  • Chromatography, Gel
  • Deuterium
  • Dimerization
  • Drug Design
  • Electrochemistry
  • Hot Temperature
  • Macromolecular Substances
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Weight
  • Peptides / chemical synthesis
  • Peptides / chemistry*
  • Protein Conformation*
  • Protein Denaturation
  • Protein Structure, Secondary*
  • Spectrometry, Fluorescence


  • Macromolecular Substances
  • Peptides
  • Deuterium