Department of Physics, Institute of Biophysics, Central China Normal University, Wuhan, 430079, China.
Department of Physics, George Washington University, Washington, DC, 20052, USA.
BMC Bioinformatics. 2021 Sep 8;22(1):428. doi: 10.1186/s12859-021-04349-4.
RNA regulates a variety of biological functions by interacting with other molecules. The ligand often binds in the RNA pocket to trigger structural changes or functions. Thus, it is essential to explore and visualize the RNA pocket to elucidate the structural and recognition mechanism for the RNA-ligand complex formation.
In this work, we developed one user-friendly bioinformatics tool, RPocket. This database provides geometrical size, centroid, shape, secondary structure element for RNA pocket, RNA-ligand interaction information, and functional sites. We extracted 240 RNA pockets from 94 non-redundant RNA-ligand complex structures. We developed RPDescriptor to calculate the pocket geometrical property quantitatively. The geometrical information was then subjected to RNA-ligand binding analysis by incorporating the sequence, secondary structure, and geometrical combinations. This new approach takes advantage of both the atom-level precision of the structure and the nucleotide-level tertiary interactions. The results show that the higher-level topological pattern indeed improves the tertiary structure prediction. We also proposed a potential mechanism for RNA-ligand complex formation. The electrostatic interactions are responsible for long-range recognition, while the Van der Waals and hydrophobic contacts for short-range binding and optimization. These interaction pairs can be considered as distance constraints to guide complex structural modeling and drug design.
RPocket database would facilitate RNA-ligand engineering to regulate the complex formation for biological or medical applications. RPocket is available at http://zhaoserver.com.cn/RPocket/RPocket.html .
RNA 通过与其他分子相互作用来调节各种生物功能。配体通常结合在 RNA 口袋中，以触发结构变化或功能。因此，探索和可视化 RNA 口袋对于阐明 RNA-配体复合物形成的结构和识别机制至关重要。
在这项工作中，我们开发了一个用户友好的生物信息学工具 RPocket。该数据库提供了 RNA 口袋的几何尺寸、质心、形状、二级结构元素、RNA-配体相互作用信息和功能位点。我们从 94 个非冗余的 RNA-配体复合物结构中提取了 240 个 RNA 口袋。我们开发了 RPDescriptor 来定量计算口袋的几何性质。然后，我们将几何信息与序列、二级结构和几何组合相结合，进行 RNA-配体结合分析。这种新方法利用了结构的原子级精度和核苷酸级别的三级相互作用。结果表明，更高层次的拓扑模式确实可以提高三级结构预测的准确性。我们还提出了一种 RNA-配体复合物形成的潜在机制。静电相互作用负责远程识别，而范德华力和疏水力则负责短程结合和优化。这些相互作用对可以被视为距离约束，以指导复杂结构建模和药物设计。
RPocket 数据库将有助于 RNA-配体工程，以调节复合物的形成，从而应用于生物学或医学领域。RPocket 可在 http://zhaoserver.com.cn/RPocket/RPocket.html 上获取。
