Distribution of tightened end fragments of globular proteins statistically matches that of topohydrophobic positions: towards an efficient punctuation of protein folding?

Cell Mol Life Sci. 2001 Mar;58(3):492-8. doi: 10.1007/pl00000873.


Using a set of 372 proteins representative of a variety of 56 distinct globular folds, a statistical correlation was observed between two recently revealed features of protein structures: tightened end fragments or 'closed loops', i.e. sequence fragments that are able in three-dimensional (3D) space to nearly close their ends (a current parameter of polymer physics), and 'topohydrophobic positions', i.e. positions always occupied in 3D space by strong hydrophobic amino acids for all members of a fold family. Indeed, in sequence space, the distribution of preferred lengths for tightened end fragments and that for topohydrophobic separation match. In addition to this statistically significant similarity, the extremities of these 'closed loops' may be preferentially occupied by topohydrophobic positions, as observed on a random sample of various folds. This observation may be of special interest for sequence comparison of distantly related proteins. It is also important for the ab initio prediction of protein folds, considering the remarkable topological properties of topohydrophobic positions and their paramount importance within folding nuclei. Consequently, topohydrophobic positions locking the 'closed loops' belong to the deep cores of protein domains and might have a key role in the folding process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Models, Molecular*
  • Models, Statistical*
  • Protein Folding*
  • Proteins / chemistry*


  • Proteins