Protein-RNA Docking Using ICM.

Protein-RNA interactions play an important role in many biological processes. Computational methods such as docking have been developed to complement existing biophysical and structural biology techniques. Computational prediction of protein-RNA complex structures includes two steps: generating candidate structures from the individual protein and RNA parts and scoring the generated poses to pick out the correct one. In this work, we considered three recently developed data sets of protein-RNA complexes to evaluate and improve the performance of the FFT-based rigid-body docking algorithm implemented in the ICM package. An electrostatic term describing interactions between negatively charged phosphate groups and positively charged protein residues was added to the energy function used during the docking step to take into account the greater role that electrostatic interactions play in protein-RNA complexes. Next, the docking results were used to optimize a scoring function including van der Waals, electrostatic, and solvation terms. This optimization yielded a much smaller weight for the solvation term indicating that solvation energy may be less important for the scoring of protein-RNA structures. Rescoring of the generated poses with the new scoring function led to much higher success rates, while pose clustering by contact fingerprints produced further improvements, achieving a success rate of 0.66 for the top 100 structures.