Nanomechanical measurements of the sequence-dependent folding landscapes of single nucleic acid hairpins

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Proceedings titleProceedings of the National Academy of Sciences of the United States of America
Conference2006 April 18
Pages61906195; # of pages: 6
AbstractNucleic acid hairpins provide a powerful model system for probing the formation of secondary structure. We report a systematic study of the kinetics and thermodynamics of the folding transition for individual DNA hairpins of varying stem length, loop length, and stem GC content. Folding was induced mechanically in a high-resolution optical trap using a unique force clamp arrangement with fast response times. We measured 20 different hairpin sequences with quasi-random stem sequences that were 6–30 bp long, polythymidine loops that were 3–30 nt long, and stem GC content that ranged from 0% to 100%. For all hairpins studied, folding and unfolding were characterized by a single transition. From the force dependence of these rates, we determined the position and height of the energy barrier, finding that the transition state for duplex formation involves the formation of 1–2 bp next to the loop. By measuring unfolding energies spanning one order of magnitude, transition rates covering six orders of magnitude, and hairpin opening distances with subnanometer precision, our results define the essential features of the energy landscape for folding. We find quantitative agreement over the entire range of measurements with a hybrid landscape model that combines thermodynamic nearest-neighbor free energies and nanomechanical DNA stretching energies.
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AffiliationNRC National Institute for Nanotechnology; National Research Council Canada
Peer reviewedYes
NRC number75
NPARC number8926585
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Record identifier9a8a50f7-42a8-48a3-8a82-ab0ac989db08
Record created2009-04-23
Record modified2016-05-09
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