Translating from Proteins to Ribonucleic Acids for Ligand-binding Site Detection

Identifying druggable ligand-binding sites on the surface of the macromolecular targets is an important process in structure-based drug discovery. Deep-learning models have been shown to successfully predict ligand-binding sites of proteins. As a step toward predicting binding sites in RNA and RNA-protein complexes, we employ three-dimensional convolutional neural networks. We introduce a dataset splitting approach to minimize structure-related bias in training data, and investigate the influence of protein-based neural network pre-training before fine-tuning on RNA structures. Models that were pre-trained on proteins considerably outperformed the models that were trained exclusively on RNA structures. Overall, 71 % of the known RNA binding sites were correctly located within 4 Å of their true centres.