Solution structure and dynamics of a de novo designed three-helix bundle protein

Proc Natl Acad Sci U S A. 1999 May 11;96(10):5486-91. doi: 10.1073/pnas.96.10.5486.


Although de novo protein design is an important endeavor with implications for understanding protein folding, until now, structures have been determined for only a few 25- to 30-residue designed miniproteins. Here, the NMR solution structure of a complex 73-residue three-helix bundle protein, alpha3D, is reported. The structure of alpha3D was not based on any natural protein, and yet it shows thermodynamic and spectroscopic properties typical of native proteins. A variety of features contribute to its unique structure, including electrostatics, the packing of a diverse set of hydrophobic side chains, and a loop that incorporates common capping motifs. Thus, it is now possible to design a complex protein with a well defined and predictable three-dimensional structure.

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
  • Cloning, Molecular
  • Escherichia coli / genetics
  • Hydrogen / metabolism
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Sequence Data
  • Peptides / chemistry
  • Protein Engineering
  • Protein Structure, Secondary
  • Proteins / chemical synthesis*
  • Proteins / chemistry*
  • Recombinant Proteins / chemistry
  • Sequence Alignment
  • Static Electricity


  • Peptides
  • Proteins
  • Recombinant Proteins
  • alpha3D protein, synthetic
  • Hydrogen

Associated data

  • PDB/2A3D