Discrete state model and accurate estimation of loop entropy of RNA secondary structures.
Discrete state model and accurate estimation of loop entropy of RNA secondary structures.
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DOI：
10.1063/1.2895050
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发表时间：
2008-03
期刊：
影响因子：
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通讯作者：
Jian Zhang;Ming Lin;Rong Chen;Wei Wang;Jie Liang
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文献类型：
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作者：
Jian Zhang;Ming Lin;Rong Chen;Wei Wang;Jie Liang
构象熵对RNA分子的稳定性和折叠有着重要的贡献，但长环构象熵的测量和计算是一个挑战。我们开发了基于已知RNA结构的RNA骨架的优化离散k状态模型，用于计算环的熵，其被建模为自避免行走。为了估计发夹，凸起，内部循环，和多分支循环的长长度（高达50）的熵，我们开发了一个有效的抽样方法的基础上顺序蒙特卡罗原理。我们的方法考虑排除体积效应。该方法具有通用性，可用于计算任意复杂度、较长循环的熵。对于短长度的环，我们的结果与最近的理论模型和实验测量是一致的。对于长循环，我们估计的发夹环的熵与Jacobson-Stockmayer外推模型非常一致。然而，对于凸起环和更复杂的二级结构，如内部和多分支环，我们发现，Jacobson-Stockmayer外推模型有很大的误差。在熵估计的基础上，我们发展了精确计算不同二级结构长环熵的经验公式。我们的研究的影响的不对称大小的循环表明，循环熵的内部循环在很大程度上是由总的循环长度，只有轻微的两个循环的不对称大小的影响。我们的研究结果表明，显着的不对称效应的环长度在内部循环测量的实验很可能是部分双折射。我们的方法可以应用于开发改进的能量参数重要的研究RNA的稳定性和折叠，并预测RNA的二级和三级结构。用于计算环路熵的离散模型和程序可以在http://gila.bioengr.uic.edu/resources/RNA.html下载。
Conformational entropy makes important contribution to the stability and folding of RNA molecule, but it is challenging to either measure or compute conformational entropy associated with long loops. We develop optimized discrete k-state models of RNA backbone based on known RNA structures for computing entropy of loops, which are modeled as self-avoiding walks. To estimate entropy of hairpin, bulge, internal loop, and multibranch loop of long length (up to 50), we develop an efficient sampling method based on the sequential Monte Carlo principle. Our method considers excluded volume effect. It is general and can be applied to calculating entropy of loops with longer length and arbitrary complexity. For loops of short length, our results are in good agreement with a recent theoretical model and experimental measurement. For long loops, our estimated entropy of hairpin loops is in excellent agreement with the Jacobson-Stockmayer extrapolation model. However, for bulge loops and more complex secondary structures such as internal and multibranch loops, we find that the Jacobson-Stockmayer extrapolation model has large errors. Based on estimated entropy, we have developed empirical formulae for accurate calculation of entropy of long loops in different secondary structures. Our study on the effect of asymmetric size of loops suggest that loop entropy of internal loops is largely determined by the total loop length, and is only marginally affected by the asymmetric size of the two loops. Our finding suggests that the significant asymmetric effects of loop length in internal loops measured by experiments are likely to be partially enthalpic. Our method can be applied to develop improved energy parameters important for studying RNA stability and folding, and for predicting RNA secondary and tertiary structures. The discrete model and the program used to calculate loop entropy can be downloaded at http://gila.bioengr.uic.edu/resources/RNA.html.