title: Ultrafast folding of alpha3D: a de novo designed three-helix bundle protein.
abstract: Here, we describe the folding/unfolding kinetics of alpha3D, a small designed three-helix bundle. Both IR temperature jump and ultrafast fluorescence mixing methods reveal a single-exponential process consistent with a minimal folding time of 3.2 +/- 1.2 micros (at approximately 50 degrees C), indicating that a protein can fold on the 1- to 5-micros time scale. Furthermore, the single-exponential nature of the relaxation indicates that the prefactor for transition state (TS)-folding models is probably >or=1 (micros)-1 for a protein of this size and topology. Molecular dynamics simulations and IR spectroscopy provide a molecular rationale for the rapid, single-exponential folding of this protein. alpha3D shows a significant bias toward local helical structure in the thermally denatured state. The molecular dynamics-simulated TS ensemble is highly heterogeneous and dynamic, allowing access to the TS via multiple pathways.
authors.affiliation: Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Yongjin
authors.initials: Y
authors.lastname: Zhu
authors.forename: Darwin O V
authors.initials: DO
authors.lastname: Alonso
authors.forename: Kosuke
authors.initials: K
authors.lastname: Maki
authors.forename: Cheng-Yen
authors.initials: CY
authors.lastname: Huang
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Lahr
authors.forename: Valerie
authors.initials: V
authors.lastname: Daggett
authors.forename: Heinrich
authors.initials: H
authors.lastname: Roder
authors.forename: William F
authors.initials: WF
authors.lastname: DeGrado
authors.forename: Feng
authors.initials: F
authors.lastname: Gai
mesh_terms: D007700:Kinetics; D008958:Models, Molecular; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D013816:Thermodynamics; D013997:Time Factors; D014508:Urea
chemical_list: D011506:Proteins; C119365:alpha3D protein, synthetic; D014508:Urea