A knowledge-based potential function predicts the specificity and relative binding energy of RNA-binding proteins

RNA–protein interactions are fundamental to gene expression. Thus, the molecular basis for the sequence dependence of protein–RNA recognition has been extensively studied experimentally. However, there have been very few computational studies of this problem, and no sustained attempt has been made towards using computational methods to predict or alter the sequence-specificity of these proteins. In the present study, we provide a distance-dependent statistical potential function derived from our previous work on protein–DNA interactions. This potential function discriminates native structures from decoys, successfully predicts the native sequences recognized by sequence-specific RNA-binding proteins, and recapitulates experimentally determined relative changes in binding energy due to mutations of individual amino acids at protein–RNA interfaces. Thus, this work demonstrates that statistical models allow the quantitative analysis of protein–RNA recognition based on their structure and can be applied to modeling protein–RNA interfaces for prediction and design purposes.