Computational modeling of RNA 3D structures, with the aid of experimental restraints.
Computational modeling of RNA 3D structures, with the aid of experimental restraints.
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DOI：
10.4161/rna.28826
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发表时间：
2014
期刊：
影响因子：
4.1
通讯作者：
Bujnicki JM
中科院分区：
文献类型：
--
作者：
Magnus M;Matelska D;Lach G;Chojnowski G;Boniecki MJ;Purta E;Dawson W;Dunin-Horkawicz S;Bujnicki JM
除了其主要功能是将遗传信息从DNA传递到蛋白质的mRNA之外，还存在许多其他类别的RNA分子，其参与各种功能，例如催化生物化学反应或执行调节作用。与蛋白质类似，RNA的功能取决于它们的结构和动力学，这在很大程度上由核糖核苷酸序列决定。高分辨率RNA结构的实验测定既费力又困难，因此，大多数已知的RNA在结构上仍然是未知的。为了解决这个问题，开发了计算结构预测方法，其模拟RNA结构形成的物理过程（“希腊科学”方法）或利用来自其他RNA分子的已知结构的信息（“巴比伦科学”方法）。所有的计算方法都受到各种限制，这使得它们对于长RNA序列的结构预测通常不可靠。然而，在许多情况下，计算和实验方法的局限性可以通过将这两种互补的方法相互结合来克服。在这项工作中，我们回顾了RNA结构预测的计算方法，重点是实现（特定程序），可以利用来自实验分析的限制。我们还列出了实验方法，其结果可以相对容易地使用计算方法。最后，我们描述了案例研究，计算和实验分析成功地结合起来，以确定RNA结构，将保持遥不可及的每一个这些方法分别应用。
In addition to mRNAs whose primary function is transmission of genetic information from DNA to proteins, numerous other classes of RNA molecules exist, which are involved in a variety of functions, such as catalyzing biochemical reactions or performing regulatory roles. In analogy to proteins, the function of RNAs depends on their structure and dynamics, which are largely determined by the ribonucleotide sequence. Experimental determination of high-resolution RNA structures is both laborious and difficult, and therefore, the majority of known RNAs remain structurally uncharacterized. To address this problem, computational structure prediction methods were developed that simulate either the physical process of RNA structure formation (“Greek science” approach) or utilize information derived from known structures of other RNA molecules (“Babylonian science” approach). All computational methods suffer from various limitations that make them generally unreliable for structure prediction of long RNA sequences. However, in many cases, the limitations of computational and experimental methods can be overcome by combining these two complementary approaches with each other. In this work, we review computational approaches for RNA structure prediction, with emphasis on implementations (particular programs) that can utilize restraints derived from experimental analyses. We also list experimental approaches, whose results can be relatively easily used by computational methods. Finally, we describe case studies where computational and experimental analyses were successfully combined to determine RNA structures that would remain out of reach for each of these approaches applied separately.