Computational Science Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata, 700064, India.
Institute of Molecular Biology gGmbH (IMB), Ackermannweg 4, 55128, Mainz, Germany.
Interdiscip Sci. 2022 Sep;14(3):759-774. doi: 10.1007/s12539-022-00528-w. Epub 2022 Jun 15.
The stable three-dimensional structure of RNA is known to play several important biochemical roles, from post-transcriptional gene regulation to enzymatic action. These structures contain double-helical regions, which often have different types of non-canonical base pairs in addition to Watson-Crick base pairs. Hence, it is important to study their structures from experimentally obtained or even predicted ones, to understand their role, or to develop a drug against the potential targets. Molecular Modeling of RNA double helices containing non-canonical base pairs is a difficult process, particularly due to the unavailability of structural features of non-Watson-Crick base pairs. Here we show a composite web-server with an associated database that allows one to generate the structure of RNA double helix containing non-canonical base pairs using consensus parameters obtained from the database. The database classification is followed by an evaluation of the central tendency of the structural parameters as well as a quantitative estimation of interaction strengths. These parameters are used to construct three-dimensional structures of double helices composed of Watson-Crick and/or non-canonical base pairs. Our benchmark study to regenerate double-helical fragments of many experimentally derived RNA structures indicate very high accuracy. This composite server is expected to be highly useful in understanding functions of various pre-miRNA by modeling structures of the molecules and estimating binding efficiency. The database can be accessed from http://hdrnas.saha.ac.in/rnabpdb .
RNA 的稳定三维结构已知在几种重要的生化作用中发挥作用，从转录后基因调控到酶促作用。这些结构包含双链区域，除了 Watson-Crick 碱基对外，通常还有不同类型的非规范碱基对。因此，从实验获得的甚至预测的结构中研究它们的结构对于理解它们的作用或开发针对潜在靶标的药物非常重要。含有非规范碱基对的 RNA 双螺旋的分子建模是一个困难的过程，特别是由于非 Watson-Crick 碱基对的结构特征不可用。在这里，我们展示了一个具有相关数据库的组合网络服务器，该服务器允许使用从数据库中获得的共识参数生成含有非规范碱基对的 RNA 双螺旋结构。数据库分类后，评估结构参数的中心趋势以及相互作用强度的定量估计。这些参数用于构建由 Watson-Crick 和/或非规范碱基对组成的双链的三维结构。我们对许多实验衍生的 RNA 结构的双链片段进行再生的基准研究表明，准确性非常高。该组合服务器有望通过对分子结构进行建模并估计结合效率，在理解各种前体 miRNA 的功能方面非常有用。该数据库可从 http://hdrnas.saha.ac.in/rnabpdb 访问。
