期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 114, 期 6, 页码 1329-1334出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1611602114
关键词
folding; DNA hairpins; energy landscapes; optical tweezers
资金
- Natural Sciences and Engineering Research Council of Canada
- National Research Council
- Alberta Innovates Technology Futures
The conformational diffusion coefficient, D, sets the timescale for microscopic structural changes during folding transitions in biomolecules like nucleic acids and proteins. D encodes significant information about the folding dynamics such as the roughness of the energy landscape governing the folding and the level of internal friction in the molecule, but it is challenging to measure. The most sensitive measure of D is the time required to cross the energy barrier that dominates folding kinetics, known as the transition path time. To investigate the sequence dependence of D in DNA duplex formation, we measured individual transition paths from equilibrium folding trajectories of single DNA hairpins held under tension in high-resolution optical tweezers. Studying hairpins with the same helix length but with G: C base-pair content varying from 0 to 100%, we determined both the average time to cross the transition paths, tau(tp), and the distribution of individual transit times, P-TP(t). We then estimated D from both tau(tp) and P-TP(t) from theories assuming one-dimensional diffusive motion over a harmonic barrier. tau(tp) decreased roughly linearly with the G: C content of the hairpin helix, being 50% longer for hairpins with only A: T base pairs than for those with only G: C base pairs. Conversely, D increased linearly with helix G: C content, roughly doubling as the G: C content increased from 0 to 100%. These results reveal that G: C base pairs form faster than A: T base pairs because of faster conformational diffusion, possibly reflecting lower torsional barriers, and demonstrate the power of transition path measurements for elucidating the microscopic determinants of folding.
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