DrugPred_RNA – Structure-Based Druggability Predictions for RNA Binding Sites

Abstract

RNA is an emerging target for drug discovery.<sup> </sup>However, like for proteins, not all RNA binding sites are equally suited to be addressed with conventional drug-like ligands. To this end, we have developed the structure-based druggability predicator DrugPred_RNA to identify druggable RNA binding sites. Due to the paucity of annotated RNA binding sites, the predictor was trained on protein pockets, albeit using only descriptors that can be calculated for both, RNA and protein binding sites. DrugPred_RNA performed well in discriminating druggable from less druggable binding sites for the protein set and delivered sensible predictions for selected RNA binding sites. Further, the majority of drug-like ligands contained in a data set of RNA-containing pockets were found in pockets predicted to be druggable, further adding confidence to the performance of DrugPred_RNA. The method is robust against conformational changes in the binding site and can contribute to direct drug discovery efforts for RNA targets