Turning limited experimental information into 3D models of RNA
Turning limited experimental information into 3D models of RNA
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DOI：
10.1261/rna.2112110
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发表时间：
2010-09-01
期刊：
影响因子：
4.5
通讯作者：
Altman, Russ B.
中科院分区：
文献类型：
--
作者：
Flores, Samuel Coulbourn;Altman, Russ B.
我们对RNA在细胞中的功能的理解正在迅速发展。至于蛋白质，RNA的详细三维（3D）结构往往是了解其功能的关键。尽管晶体学和核磁共振（NMR）可以确定一些RNA结构的原子坐标，但许多3D结构存在技术挑战，使这些方法难以应用。RNA的巨大柔韧性、带电荷的主链、缺乏特定的表面特征以及倾向于形成动力学陷阱，这些都与它的长折叠时间相结合，对基于物理折叠的硅方法构成了挑战。另一方面，碱基配对相互作用（形成螺旋或孤立的三级接触）和基序通常可以从相对低成本的实验或信息学分析中获得。我们提出了rnabbuilder，这是一种新颖的代码，它使用内部坐标力学来满足用户指定的碱基配对和化学约束下的立体力。该代码概括了tRNA的拓扑结构和特征l形，并获得了四膜虫核酶P4/P6结构域的精确非晶体结构。该算法几乎与分子大小成线性关系，为更大结构的建模打开了大门。
Our understanding of RNA functions in the cell is evolving rapidly. As for proteins, the detailed three-dimensional (3D) structure of RNA is often key to understanding its function. Although crystallography and nuclear magnetic resonance (NMR) can determine the atomic coordinates of some RNA structures, many 3D structures present technical challenges that make these methods difficult to apply. The great flexibility of RNA, its charged backbone, dearth of specific surface features, and propensity for kinetic traps all conspire with its long folding time, to challenge in silico methods for physics-based folding. On the other hand, base-pairing interactions (either in runs to form helices or isolated tertiary contacts) and motifs are often available from relatively low-cost experiments or informatics analyses. We present RNABuilder, a novel code that uses internal coordinate mechanics to satisfy user-specified base pairing and steric forces under chemical constraints. The code recapitulates the topology and characteristic L-shape of tRNA and obtains an accurate noncrystallographic structure of the Tetrahymena ribozyme P4/P6 domain. The algorithm scales nearly linearly with molecule size, opening the door to the modeling of significantly larger structures.