Flexible Docking of Protein-Nucleic Acid Complexes

蛋白质-RNA相互作用对于许多生物过程是必不可少的。准确理解这些过程需要了解参与的三维蛋白质-RNA复合物结构。在该项目期间，Zacharias小组开发的高效灵活的计算蛋白质-蛋白质对接方法Attract将被扩展到允许蛋白质-RNA对接。将采用与吸引方法中采用的简化蛋白质模型在精神上类似的已经开发的简化RNA模型。计划改进和优化蛋白质-RNA相互作用的评分函数，并在大量可用的蛋白质-RNA复合物上对其进行测试。此外，配偶体结构的构象灵活性将通过已经成功测试蛋白质-蛋白质对接的方法来考虑，例如通过多个构象拷贝或沿着沿着预先计算的软集体自由度的结构松弛来表示柔性部分。该方法将被应用到一些蛋白质-RNA复合物的生物学重要性，没有实验复杂的结构。此外，我们将分析蛋白质-RNA和核糖体中的RNA-RNA相互作用的界面结构，作为大型蛋白质-RNA组装的一个例子。在界面区域包含序列变异和协变将有助于提高评分函数，并将为界面的进化提供新的见解，并可能对核糖体的有序组装过程提供新的见解。

Protein-RNA interactions are essential for many biological processes. An accurate understanding of these processes requires knowledge of the participating three-dimensional protein-RNA complex structures. During the project the efficient flexible computational protein-protein docking approach Attract developed by the Zacharias group will be extended to allow protein-RNA docking. An already developed reduced RNA model in spirit similar to the reduced protein model employed in the Attract approach will be employed. It is planned to refine and optimize a scoring function for protein-RNA interactions and to test it on a large set of available protein-RNA complexes. Furthermore, conformational flexibility of partner structures will be considered by methods already successfully tested for protein-protein docking such as representation of flexible parts by multiple conformational copies or structural relaxation along pre-calculated soft collective degrees of freedom. The methodology will be applied to a number of protein-RNA complexes of biological importance for which no experimental complex structure is available. In addition, we will analyse the interface structure of protein-RNA and RNA-RNA interactions in the ribosome as an example of a large protein-RNA assembly. The inclusion of sequence variation and covariation at the interface regions will help to improve the scoring function and will give new insights into the evolution of the interfaces and possibly on the ordered assembly process of the ribosome.