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    Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15486-91. Epub 2003 Dec 11.

    Ultrafast folding of alpha3D: a de novo designed three-helix bundle protein.

    Zhu Y, Alonso DO, Maki K, Huang CY, Lahr SJ, Daggett V, Roder H, DeGrado WF, Gai F.

    Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA.

    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.

    PMID: 14671331 [PubMed - indexed for MEDLINE]

    PMCID: 307594

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