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Intrinsically-disordered regions lack a well-defined 3D structure, but play key roles in determining the function of many proteins. Although predictors of disorder have been shown to achieve relatively high rates of correct classification of these segments, improvements over the the years have been slow, and accurate methods are needed that are capable of accommodating the ever-increasing amount of structurally-determined protein sequences to try to boost predictive performances. In this paper, we propose a predictor for short disordered regions based on bidirectional recurrent neural networks and tested by rigorous five-fold cross-validation on a large, non-redundant dataset collected from MobiDB, a new comprehensive source of protein disorder annotations. The system exploits sequence and structural information in the forms of frequency profiles, predicted secondary structure and solvent accessibility and direct disorder annotations from homologous protein structures (templates) deposited in the Protein Data Bank. The contributions of sequence, structure and homology information result in large improvements in predictive accuracy. Additionally, the large scale of the training set leads to low false positive rates, making our systems a robust and efficient way to address high-throughput disorder prediction.

international journal of molecular sciences

Accurate Ab Initio and Template-Based Prediction of Short Intrinsically-Disordered Regions by Bidirectional Recurrent Neural Networks Trained on Large-Scale Datasets