Direct measurement of the full, sequence-dependent folding landscape of a nucleic acid

Direct measurement of the full, sequence-dependent folding landscape of a nucleic acid
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DOI:
10.1126/science.1133601
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发表时间:
2006-11-10
期刊:
影响因子:
56.9
通讯作者:
Block, Steven M.
Block, Steven M.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Woodside, Michael T.;Anthony, Peter C.;Block, Steven M.

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核酸发夹提供了一个强大的模型系统,了解大分子折叠,自由能景观,可以很容易地通过改变发夹序列操纵。通过对高分辨率单分子轨道的解卷积,获得了在光学力钳施加的受控载荷下DNA发夹结构可逆折叠的能量景观的完整形状。发夹折叠能垒的位置和高度可以通过调节G:C碱基对的数量和位置来调节,折叠中间体的存在和位置可以通过引入单核苷酸错配来控制。
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.