Modeling RNA folding paths with pseudoknots: Application to hepatitis delta virus ribozyme
Modeling RNA folding paths with pseudoknots: Application to hepatitis delta virus ribozyme
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DOI：
10.1073/pnas.110533697
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发表时间：
2000-06-06
影响因子：
11.1
通讯作者：
Siggia, ED
中科院分区：
文献类型：
--
作者：
Isambert, H;Siggia, ED
核酸杂交的定量理解对于生物技术的许多方面是必不可少的，例如DNA微阵列，以及RNA的结构和折叠动力学。然而，核酸二级结构的预测长期以来一直受到环内部螺旋的存在的阻碍，所谓的假结，其施加复杂的三维构象约束。在本文中，我们计算的伪结自由能分析已知的标准参数，我们展示了如何可以包括在一个动力学蒙特卡罗代码的结果，按照淬火或顺序折叠过程中的二级结构的继承。对于丁型肝炎病毒核酶，我们预测几个非原生茎的折叠路径上，表征动力学捕获状态，解释几个实验表征的突变的折叠路径，并建议如何与基因组的其他部分杂交灭活新形成的核酶。
A quantitative understanding of nucleic: acid hybridization is essential to many aspects of biotechnology, such as DNA microarrays, as well as to the structure and folding kinetics of RNA. However, predictions of nucleic acid secondary structures have long been impeded by the presence of helices interior to loops, so-called pseudoknots, which impose complex three-dimensional conformational constraints. In this paper we compute the pseudoknot free energies analytically in terms of known standard parameters, and we show how the results can be included in a kinetic Monte Carlo code to follow the succession of secondary structures during quenched or sequential folding. For the hepatitis delta virus ribozyme, we predict several nonnative stems on the folding path, characterize a kinetically trapped state, interpret several experimentally characterized mutations in terms of the folding path, and suggest how hybridization with other parts of the genome inactivates the newly formed ribozyme.