TY - JOUR
T1 - Atomically detailed description of the unfolding of α-lactalbumin by the combined use of experiments and simulations
AU - Oroguchi, Tomotaka
AU - Ikeguchi, Mitsunori
AU - Saeki, Kimiko
AU - Kamagata, Kiyoto
AU - Sawano, Yoriko
AU - Tanokura, Masaru
AU - Kidera, Akinori
AU - Kuwajima, Kunihiro
PY - 2005/11/18
Y1 - 2005/11/18
N2 - The recombinant form of goat α-lactalbumin has a significantly faster unfolding rate compared to the authentic form, although the two molecules differ only in an extra methionine at the N terminus of the recombinant. The mechanism of the destabilization caused by this residue was investigated through the combined use of kinetic experiments and molecular dynamics simulations. Unfolding simulations for the authentic and recombinant forms at 398 K (ten trajectories of 5 ns for each form, 100 ns total) precisely reproduced the experimentally observed differences in unfolding behavior. In addition, experiments reproduced the destabilization of a mutant protein, T38A, faithfully as predicted by the simulations. This bidirectional verification between experiments and simulations enabled the atomically detailed description of the role of the extra methionine residue in the unfolding process.
AB - The recombinant form of goat α-lactalbumin has a significantly faster unfolding rate compared to the authentic form, although the two molecules differ only in an extra methionine at the N terminus of the recombinant. The mechanism of the destabilization caused by this residue was investigated through the combined use of kinetic experiments and molecular dynamics simulations. Unfolding simulations for the authentic and recombinant forms at 398 K (ten trajectories of 5 ns for each form, 100 ns total) precisely reproduced the experimentally observed differences in unfolding behavior. In addition, experiments reproduced the destabilization of a mutant protein, T38A, faithfully as predicted by the simulations. This bidirectional verification between experiments and simulations enabled the atomically detailed description of the role of the extra methionine residue in the unfolding process.
KW - Equilibrium experiments
KW - Kinetic experiments
KW - Molecular dynamics simulations
KW - Protein unfolding
KW - Unfolding dynamics
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U2 - 10.1016/j.jmb.2005.09.061
DO - 10.1016/j.jmb.2005.09.061
M3 - Article
C2 - 16236317
AN - SCOPUS:27344435115
VL - 354
SP - 164
EP - 172
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
SN - 0022-2836
IS - 1
ER -