Flexible Docking of Protein-Nucleic Acid Complexes

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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.