Understanding the role of the topology in protein folding by computational inverse folding experiments

Antonio Mucherino, Susan Costantini, Daniela di Serafino, Marco D'Apuzzo, Angelo Facchiano, Giovanni Colonna

Research output: Contribution to journalArticlepeer-review


Recent studies suggest that protein folding should be revisited as the emergent property of a complex system and that the nature allows only a very limited number of folds that seem to be strongly influenced by geometrical properties. In this work we explore the principles underlying this new view and show how helical protein conformations can be obtained starting from simple geometric considerations. We generated a large data set of C-alpha traces made of 65 points, by computationally solving a backbone model that takes into account only topological features of the all-alpha proteins; then, we built corresponding tertiary structures, by using the sequences associated to the crystallographic structures of four small globular all-alpha proteins from PDB, and analysed them in terms of structural and energetic properties. In this way we obtained four poorly populated sets of structures that are reasonably similar to the conformational states typical of the experimental PDB structures. These results show that our computational approach can capture the native topology of all-alpha proteins; furthermore, it generates backbone folds without the influence of the side chains and uses the protein sequence to select a specific fold among the generated folds. This agrees with the recent view that the backbone plays an important role in the protein folding process and that the amino acid sequence chooses its own fold within a limited total number of folds.

Original languageEnglish
Pages (from-to)233-239
Number of pages7
JournalComputational Biology and Chemistry
Issue number4
Publication statusPublished - Aug 2008


  • All-alpha proteins
  • Computational method
  • Global optimization model
  • Protein fold
  • Protein folding
  • Topology

ASJC Scopus subject areas

  • Biochemistry
  • Structural Biology
  • Analytical Chemistry
  • Physical and Theoretical Chemistry


Dive into the research topics of 'Understanding the role of the topology in protein folding by computational inverse folding experiments'. Together they form a unique fingerprint.

Cite this