De novo design of helical bundles as models for understanding protein folding and function

Acc Chem Res. 2000 Nov;33(11):745-54. doi: 10.1021/ar970004h.


De novo protein design has proven to be a powerful tool for understanding protein folding, structure, and function. In this Account, we highlight aspects of our research on the design of dimeric, four-helix bundles. Dimeric, four-helix bundles are found throughout nature, and the history of their design in our laboratory illustrates our hierarchic approach to protein design. This approach has been successfully applied to create a completely native-like protein. Structural and mutational analysis allowed us to explore the determinants of native protein structure. These determinants were then applied to the design of a dinuclear metal-binding protein that can now serve as a model for this important class of proteins.

Publication types

  • Review

MeSH terms

  • Chemical Phenomena
  • Chemistry, Physical
  • Protein Folding*
  • Protein Structure, Secondary*
  • Proteins / chemical synthesis*
  • Proteins / chemistry


  • Proteins