MODELING THE 3-DIMENSIONAL STRUCTURE OF RNA USING DISCRETE NUCLEOTIDE CONFORMATIONAL SETS
MODELING THE 3-DIMENSIONAL STRUCTURE OF RNA USING DISCRETE NUCLEOTIDE CONFORMATIONAL SETS
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DOI：
10.1006/jmbi.1993.1104
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发表时间：
1993-02-20
影响因子：
5.6
通讯作者：
CEDERGREN, R
中科院分区：
文献类型：
--
作者：
GAUTHERET, D;MAJOR, F;CEDERGREN, R
核酸分子中7个扭转角的伸缩性是RNA分子计算机模拟的一个严重障碍。RNA构象搜索的计算可行性可以通过为每个核苷酸分配一组离散构象来增强。在这项工作中，四种类型的离散构象集的原子表示的核苷酸结构的定义和评估。这些集合，包括10和30之间的构象，进行了测试，以复制已知的RNA结构，并产生响应新的规格结构的能力。用MC-SYM程序进行构象搜索，该程序允许在给定的离散空间中生成满足预定的三维约束集的所有结构。已知的发夹环结构的结果表明，均方根偏差约1·5毫米的骨干原子和约2？可以预期，在模型化和X射线晶体结构之间的所有原子的0 π。给出测试结构的最忠实表示的构象集基于从结构数据库导出的核苷酸构象的分类。代表性的构象是从每个类别中选择的，这些类别充分采样了主链方向、糖皱褶和碱基取向的变化。有了这个构象集，测试发夹结构的大部分重要特征都能逼真地再现，这表明可以从离散核苷酸构象和快速系统地扫描预定义构象空间的算法的组合中构建生物学上有用的模型。
The flexibility about seven torsion angles in nucleotides constitutes a severe obstacle to computer modeling of RNA. The computational feasibility of RNA conformational searches can be enhanced by assigning to each nucleotide a set of discrete conformations. In this work, four types of discrete conformational sets for the atomic representation of nucleotide structures were defined and evaluated. These sets, comprising between 10 and 30 conformations, were tested for their ability to reproduce known RNA structures and to generate structures responding to new specifications. Conformational searches were performed with the MC-SYM program, which allows for the generation of all structures satisfying a predetermined set of three-dimensional constraints in a given discrete space. Results with known hairpin loop structures show that root-mean-square deviations of about 1·5 Å for backbone atoms and about 2?0 Å for all atoms between the modeled and X-ray crystal structures can be expected. The conformational set that gives the most faithful representation of test structures is based on the classification of nucleotide conformations derived from a structural database. Representative conformations are selected from each class that adequately sample variations in backbone direction, sugar pucker and base orientation. With this conformational set, most of the important features of test hairpin structures are reproduced with fidelity, indicating that biologically useful models can be constructed from the combination of discrete nucleotide conformations and an algorithm that rapidly and systematically scans the pre-defined conformational space.