Cao Song, Chen Shi-Jie
Department of Physics, University of Missouri, Columbia, 65211, USA.
RNA. 2009 Apr;15(4):696-706. doi: 10.1261/rna.1429009. Epub 2009 Feb 23.
RNA pseudoknots play a critical role in RNA-related biology from the assembly of ribosome to the regulation of viral gene expression. A predictive model for pseudoknot structure and stability is essential for understanding and designing RNA structure and function. A previous statistical mechanical theory allows us to treat canonical H-type RNA pseudoknots that contain no intervening loop between the helices (see S. Cao and S.J. Chen [2006] in Nucleic Acids Research, Vol. 34; pp. 2634-2652). Biologically significant RNA pseudoknots often contain interhelix loops. Predicting the structure and stability for such more-general pseudoknots remains an unsolved problem. In the present study, we develop a predictive model for pseudoknots with interhelix loops. The model gives conformational entropy, stability, and the free-energy landscape from RNA sequences. The main features of this new model are the computation of the conformational entropy and folding free-energy base on the complete conformational ensemble and rigorous treatment for the excluded volume effects. Extensive tests for the structural predictions show overall good accuracy with average sensitivity and specificity equal to 0.91 and 0.91, respectively. The theory developed here may be a solid starting point for first-principles modeling of more complex, larger RNAs.
RNA假结在从核糖体组装到病毒基因表达调控等与RNA相关的生物学过程中发挥着关键作用。假结结构和稳定性的预测模型对于理解和设计RNA的结构与功能至关重要。先前的统计力学理论使我们能够处理螺旋之间不包含间隔环的典型H型RNA假结（见《核酸研究》2006年第34卷S. Cao和S.J. Chen的文章，第2634 - 2652页）。具有生物学意义的RNA假结通常包含螺旋间环。预测此类更一般假结的结构和稳定性仍然是一个未解决的问题。在本研究中，我们开发了一种针对具有螺旋间环的假结的预测模型。该模型可根据RNA序列给出构象熵、稳定性和自由能景观。这个新模型的主要特点是基于完整的构象系综计算构象熵和折叠自由能，并对排除体积效应进行严格处理。对结构预测的广泛测试表明整体准确性良好，平均灵敏度和特异性分别为0.91和0.91。这里开发的理论可能是对更复杂、更大的RNA进行第一性原理建模的坚实起点。
