Direct measurement of the full, sequence-dependent folding landscape of a nucleic acid.
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.
Woodside
Michael T
MT
National Institute for Nanotechnology, National Research Council of Canada, Edmonton AB, Canada, T6G 2M9.
Anthony
Peter C
PC
Behnke-Parks
William M
WM
Larizadeh
Kevan
K
Herschlag
Daniel
D
Block
Steven M
SM
D020137:Base Pair Mismatch; D020029:Base Pairing; D004247:DNA / Q000737:chemistry*; D008956:Models, Chemical; D009690:Nucleic Acid Conformation; D013816:Thermodynamics
D004247:DNA