Computing the partition function for kinetically trapped RNA secondary structures.
Computing the partition function for kinetically trapped RNA secondary structures.
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DOI：
10.1371/journal.pone.0016178
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发表时间：
2011-01-28
期刊：
影响因子：
3.7
通讯作者：
Clote P
中科院分区：
文献类型：
--
作者：
Lorenz WA;Clote P
如果不存在可以通过添加或去除单个碱基对获得的较低能量结构，则RNA二级结构是局部最优的，其中能量是根据广泛接受的特纳最近邻模型定义的。局部最优结构形成动力学陷阱，因为任何偏离局部最优结构的演化都必须涉及能量上不利的折叠步骤。在这里，我们提出了一种新颖、高效的算法来计算给定 RNA 序列的所有局部最优二级结构的配分函数。我们的软件 RNAlocopt 在时间和空间中运行。此外，RNAlocopt 从所有局部最优结构的玻尔兹曼子系综中采样用户指定数量的结构。我们应用 RNAlocopt 来证明 (1) 局部最优结构的数量远少于结构总数——实际上，局部最优结构的数量大约等于所有结构数量的平方根，(2) 该子系综的结构多样性可能与整个玻尔兹曼系综的结构多样性相似或完全不同，这种情况取决于输入 RNA 的类型，(3) 通过考虑局部最优的碱基配对频率来计算（修改的）最大预期精度结构结构，是比其他当前基于热力学的方法更准确的天然结构预测。 RNAlocopt 软件是我们研究 RNA 二级结构折叠景观的一项技术突破。第一次可以快速生成长 RNA 序列的局部最优结构（特纳能量模型中的动力学陷阱），这在以前使用穷举计数的方法是不可能的。使用局部最优结构可以实现最先进的二级结构预测，以涉及最小自由能和最大预期精度计算的方法为基准。 Web 服务器和源代码可在 http://bioinformatics.bc.edu/clotelab/RNAlocopt/ 获取。
An RNA secondary structure is locally optimal if there is no lower energy structure that can be obtained by the addition or removal of a single base pair, where energy is defined according to the widely accepted Turner nearest neighbor model. Locally optimal structures form kinetic traps, since any evolution away from a locally optimal structure must involve energetically unfavorable folding steps. Here, we present a novel, efficient algorithm to compute the partition function over all locally optimal secondary structures of a given RNA sequence. Our software, RNAlocopt runs in time and space. Additionally, RNAlocopt samples a user-specified number of structures from the Boltzmann subensemble of all locally optimal structures. We apply RNAlocopt to show that (1) the number of locally optimal structures is far fewer than the total number of structures – indeed, the number of locally optimal structures approximately equal to the square root of the number of all structures, (2) the structural diversity of this subensemble may be either similar to or quite different from the structural diversity of the entire Boltzmann ensemble, a situation that depends on the type of input RNA, (3) the (modified) maximum expected accuracy structure, computed by taking into account base pairing frequencies of locally optimal structures, is a more accurate prediction of the native structure than other current thermodynamics-based methods. The software RNAlocopt constitutes a technical breakthrough in our study of the folding landscape for RNA secondary structures. For the first time, locally optimal structures (kinetic traps in the Turner energy model) can be rapidly generated for long RNA sequences, previously impossible with methods that involved exhaustive enumeration. Use of locally optimal structure leads to state-of-the-art secondary structure prediction, as benchmarked against methods involving the computation of minimum free energy and of maximum expected accuracy. Web server and source code available at http://bioinformatics.bc.edu/clotelab/RNAlocopt/.
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DOI：
10.1093/bioinformatics/btp250
发表时间：
2009-08-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Darty K;Denise A;Ponty Y
通讯作者：
Ponty Y
影响因子：
14.9
作者：
Ding, Y;Chan, CY;Lawrence, CE
通讯作者：
Lawrence, CE
影响因子：
1.8
作者：
HOFACKER, IL;FONTANA, W;SCHUSTER, P
通讯作者：
SCHUSTER, P
影响因子：
1.7
作者：
Clote, P.
通讯作者：
Clote, P.
影响因子：
2.9
作者：
BANERJEE, AR;JAEGER, JA;TURNER, DH
通讯作者：
TURNER, DH