A detailed unfolding pathway of a (β/α)8-barrel protein as studied by molecular dynamics simulations

Satoshi Akanuma, Hiroh Miyagawa, Kunihiro Kitamura, Akihiko Yamagishi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


The (β/α)8-barrel is the most common protein fold. Similar structural properties for folding intermediates of (β/α) 8-barrel proteins involved in tryptophan biosynthesis have been reported in a number of experimental studies; these intermediates have the last two β-strands and three α-helices partially unfolded, with other regions of the polypeptide chain native-like in conformation. To investigate the detailed folding/unfolding pathways of these (β/α) 8-barrel proteins, temperature-induced unfolding simulations of N-(5′-phosphoribosyl)anthranilate isomerase from Escherichia coli were carried out using a special-purpose parallel computer system. Unfolding simulations at five different temperatures showed a sequential unfolding pathway comprised of several events. Early events in unfolding involved disruption of the last two strands and three helices, producing an intermediate ensemble similar to those detected in experimental studies. Then, denaturation of the first two βα units and separation of the sixth strand from the fifth took place independently. The remaining central βαβαβ module persisted the longest during all simulations, suggesting an important role for this module as the incipient folding scaffold. Our simulations also predicted the presence of a nucleation site, onto which several hydrophobic residues condensed forming the foundation for the central βαβ αβ module.

Original languageEnglish
Pages (from-to)538-546
Number of pages9
JournalProteins: Structure, Function and Genetics
Issue number3
Publication statusPublished - 2005 Feb 15
Externally publishedYes


  • Folding intermediate
  • Folding scaffold
  • Nucleation site
  • Thermal unfolding
  • Tryptophan biosynthesis
  • βα unit

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology


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