折叠(DSP实现)
能源景观
核酸
化学
动力学
化学物理
DNA
循环(图论)
结晶学
平均力势
生物物理学
分子动力学
物理
生物
计算化学
生物化学
工程类
电气工程
组合数学
量子力学
数学
作者
Michael T. Woodside,William M. Behnke-Parks,Kevan Larizadeh,Kevin Travers,Daniel Herschlag,Steven M. Block
标识
DOI:10.1073/pnas.0511048103
摘要
Nucleic 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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