title: Unfolding pathways of goat alpha-lactalbumin as revealed in multiple alignment of molecular dynamics trajectories.
abstract: Molecular dynamics simulations of protein unfolding were performed at an elevated temperature for the authentic and recombinant forms of goat alpha-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 Phi-value analysis.
authors.affiliation: Department of Physics, Graduate School of Science, University of Tokyo, Hongo, Tokyo 113-0033, Japan.
authors.forename: Tomotaka
authors.initials: T
authors.lastname: Oroguchi
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Ikeguchi
authors.forename: Motonori
authors.initials: M
authors.lastname: Ota
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Kuwajima
authors.forename: Akinori
authors.initials: A
authors.lastname: Kidera
mesh_terms: D000818:Animals; D006041:Goats; D007700:Kinetics; D007768:Lactalbumin / Q000737:chemistry*; D008715:Methionine / Q000737:chemistry; D008958:Models, Molecular; D015233:Models, Statistical; D008968:Molecular Conformation; D010802:Phylogeny; D011487:Protein Conformation; D011489:Protein Denaturation; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry; D013269:Stochastic Processes; D013696:Temperature
chemical_list: D011994:Recombinant Proteins; D007768:Lactalbumin; D008715:Methionine