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Science 10 November 2006:
Vol. 314. no. 5801, pp. 1001 - 1004
DOI: 10.1126/science.1133601
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Reports

Direct Measurement of the Full, Sequence-Dependent Folding Landscape of a Nucleic Acid

Michael T. Woodside,1,2 Peter C. Anthony,3 William M. Behnke-Parks,2 Kevan Larizadeh,2 Daniel Herschlag,4 Steven M. Block2,5*

Nucleic acid hairpins provide a powerful model system for understanding macromolecular folding, with free-energy landscapes that can be readily manipulated by changing the hairpin sequence. The full shapes of energy landscapes for the reversible folding of DNA hairpins under controlled loads exerted by an optical force clamp were obtained by deconvolution from high-resolution, single-molecule trajectories. The locations and heights of the energy barriers for hairpin folding could be tuned by adjusting the number and location of G:C base pairs, and the presence and position of folding intermediates were controlled by introducing single-nucleotide mismatches.

1 National Institute for Nanotechnology, National Research Council of Canada, Edmonton AB, Canada, T6G 2M9.
2 Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA.
3 Biophysics Program, Stanford University, Stanford, CA 94305, USA.
4 Department of Biochemistry, Stanford University, Stanford, CA 94305, USA.
5 Department of Applied Physics, Stanford University, Stanford, CA 94305, USA.

* To whom correspondence should be addressed. E-mail: sblock{at}stanford.edu

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