Exploring the complex folding kinetics of RNA hairpins: I. General folding kinetics analysis.
Exploring the complex folding kinetics of RNA hairpins: I. General folding kinetics analysis.
复制标题
DOI：
10.1529/biophysj.105.062935
复制
发表时间：
2006-02
影响因子：
3.4
通讯作者：
Wenbing Zhang;Shi-jie Chen
中科院分区：
文献类型：
--
作者：
Wenbing Zhang;Shi-jie Chen
根据核苷酸序列，温度和其他条件，RNA发夹折叠动力学可能非常复杂。具有广泛的合作和非合作动力学行为的复杂性来自于环的形成、错误折叠状态的破坏和限速基堆的形成之间的相互作用。利用速率常数模型和动力学簇理论，我们探索了RNA发夹折叠动力学的广阔前景。该模型是通过对几个实验测量直接测试进行验证。一般的动力学折叠机制和预测的各种折叠动力学是直接适用的，并在实验中定量测试。这项研究的结果表明：1）以前基于单个发夹的实验结果只揭示了更广泛和更复杂的RNA发夹折叠景观的一小部分; 2）即使对于像发夹这样简单的结构，也不存在通用的折叠时间尺度和途径; 3）将环的大小作为确定发夹折叠速率的唯一因素是一种过度简化。
Depending on the nucleotide sequence, the temperature, and other conditions, RNA hairpin-folding kinetics can be very complex. The complexity with a wide range of cooperative and noncooperative kinetic behaviors arises from the interplay between the formation of the loops, the disruption of the misfolded states, and the formation of the rate-limiting base stacks. With a rate constant model and a kinetic-cluster theory, we explore the broad landscape for RNA hairpin-folding kinetics. The model is validated through direct tests against several experimental measurements. The general kinetic folding mechanisms and the predicted great variety of folding kinetics are directly applicable and quantitatively testable in experiments. The results from this study suggest that 1), previous experimental findings based on the individual hairpins revealed only a small fraction of much broader and more complex RNA hairpin-folding landscapes; 2), even for structures as simple as hairpins, universal folding timescales and pathways do not exist; and 3), to treat the loop size as the sole factor to determine the hairpin-folding rate is an oversimplification.