Unfolding Pathways of Goat α-Lactalbumin as Revealed in Multiple Alignment of Molecular Dynamics Trajectories

Tomotaka Oroguchi, Mitsunori Ikeguchi, Motonori Ota, Kunihiro Kuwajima, Akinori Kidera

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4 Citations (Scopus)

Abstract

Molecular dynamics simulations of protein unfolding were performed at an elevated temperature for the authentic and recombinant forms of goat α-lactalbumin. Despite very similar three-dimensional structures, the two forms have significantly different unfolding rates due to an extra N-terminal methionine in the recombinant protein. To identify subtle differences between the two forms in the highly stochastic kinetics of unfolding, we classified the unfolding trajectories using the multiple alignment method based on the analogy between the biological sequences and the molecular dynamics trajectories. A dendrogram derived from the multiple trajectory alignment revealed a clear difference in the unfolding pathways of the authentic and recombinant proteins, i.e. the former reached the transition state in an all-or-none manner while the latter unfolded less cooperatively. It was also found in the classification that the two forms of the protein shared a common transition state structure, which was in excellent agreement with the transition state structure observed experimentally in the Φ-value analysis.

Original languageEnglish
Pages (from-to)1354-1364
Number of pages11
JournalJournal of Molecular Biology
Volume371
Issue number5
DOIs
Publication statusPublished - 2007 Aug 31

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Keywords

  • molecular dynamics simulation
  • protein unfolding pathway
  • trajectory alignment
  • transition state
  • Φ-value

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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