Protein intrinsic disorder prediction using Attention U-Net and ProtTrans protein language model

The prediction of intrinsic disorder regions has significant implications for understanding protein function, structure, and dynamics. It can help to discover novel functions or protein-protein interactions essential to designing new drugs, therapies, or enzymes. Recently, a new generation of predictors based on protein language models is emerging. These algorithms reach state-of-the-art accuracy without calculating time-consuming multiple sequence alignments (MSAs). The article pre-sents a new protein intrinsic disorder predictor DisorderUnetLM based on the Attention U-Net convolutional neural network using features from the protein language model ProtTrans. DisorderUnetLM shows top results in the direct comparison with flDPnn and IDP-CRF predictors using MSAs and with the SETH predictor using features from the same ProtTrans model. Moreover, among 41 predictors from the latest Critical Assessment of Protein Intrinsic Disorder Prediction (CAID-2) benchmark, it ranks 9th for the Disorder-PDB subset (with ROC-AUC of 0.924) and 1st for the Disorder-NOX subset (with ROC-AUC of 0.844) which confirms its potential to perform well in the upcoming CAID-3 challenge for which Disor-derUnetLM was submitted.