title: The Fast-Folding Mechanism of Villin Headpiece Subdomain Studied by Multiscale Distributed Computing.
abstract: The fast-folding mechanism of a 35-residue mini-protein, villin headpiece subdomain (HP35), was investigated using folding free energy landscape analysis with the multiscale free energy landscape calculation method (MSFEL). A major and a minor folding pathway were deduced from the folding free energy landscape. In the major folding pathway, the formation of helices II and III was the rate-limiting step in the transition to an intermediate state, triggered by the folding of the PLWK motif. HP35 then folds into the native structure through the formation of the hydrophobic core located at the center of the three-helix bundle. Mutations in the motif and hydrophobic core that suppressed folding into the native state drastically changed the folding free energy landscape compared to the wild type protein. In the minor folding pathway, nucleation of the hydrophobic core preceded formation of the motif.
authors.affiliation: Department of Physics, Graduate School of Science, The University of Tokyo, Tokyo, 7-3-1, Hongo, Bunkyo-ku 113-0033, Japan.|Institute of Molecular and Cellular Bioscience, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.|Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Ryuhei
authors.initials: R
authors.lastname: Harada
authors.affiliation: Department of Physics, Graduate School of Science, The University of Tokyo, Tokyo, 7-3-1, Hongo, Bunkyo-ku 113-0033, Japan.|Institute of Molecular and Cellular Bioscience, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.|Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Kitao