Highly accurate and high-resolution function prediction of RNA binding proteins by fold recognition and binding...

A full understanding of the mechanism of post- transcriptional regulation requires more than simple two- state prediction (binding or not binding) for RNA binding proteins. Here we report a sequence-based technique dedicated for predicting complex structures of protein and RNA by combining fold recognition with binding affinity prediction. The method not only provides a highly accurate complex structure prediction (77% of residues are within 4°A RMSD from native in average for the independent test set) but also achieves the best performing two-state binding or non-binding prediction with an accuracy of 98%, precision of 84%, and Mathews correlation coefficient (MCC) of 0.62. Moreover, it predicts binding residues with an accuracy of 84%, precision of 66% and MCC value of 0.51. In addition, it has a success rate of 77% in predicting RNA binding types (mRNA, tRNA or rRNA). We further demonstrate that it makes more than 10% improvement either in precision or sensitivity than PSI- BLAST, HHPRED and our previously developed structure- based technique. This method expects to be useful for highly accurate genome-scale, high-resolution prediction of RNA-binding proteins and their complex structures. A web server (SPOT) is freely available for academic users at http://sparks.informatics.iupui.edu.