The designability of protein structures

Robert Helling, Hao Li, Régis Mélin, Jonathan Miller, Ned Wingreen, Chen Zeng, Chao Tang

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


It has been noted that natural proteins adapt only a limited number of folds. Several researchers have investigated why and how nature has selected this small number of folds. Using simple models of protein folding, we demonstrate systematically that there is a "designability principle" behind nature's selection of protein folds. The designability of a structure (fold) is measured by the number of sequences that can design the structure - that is, sequences that possess the structure as their unique ground state. Structures differ drastically in terms of their designability. A small number of highly designable structures emerge with a number of associated sequences much larger than the average. These highly designable structures possess proteinlike secondary structures, motifs, and even tertiary symmetries. In addition, they are thermodynamically more stable and fold faster than other structures. These results suggest that protein structures are selected in nature because they are readily designed and stable against mutations, and that such a selection simultaneously leads to thermodynamic stability.

Original languageEnglish (US)
Pages (from-to)157-167
Number of pages11
JournalJournal of Molecular Graphics and Modelling
Issue number1
StatePublished - 2001

All Science Journal Classification (ASJC) codes

  • Materials Chemistry
  • Spectroscopy
  • Physical and Theoretical Chemistry
  • Computer Graphics and Computer-Aided Design


  • Designability
  • Enumeration
  • Lattice models
  • Off-lattice models
  • protein folding


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