AttentiveDist: Protein Inter-Residue Distance Prediction Using Deep Learning with Attention on Quadruple Multiple Sequence Alignments

ABSTRACT Protein 3D structure prediction has advanced significantly in recent years due to improving contact prediction accuracy. This improvement has been largely due to deep learning approaches that predict inter-residue contacts and, more recently, distances using multiple sequence alignments (MSAs). In this work we present AttentiveDist, a novel approach that uses different MSAs generated with different E-values in a single model to increase the co-evolutionary information provided to the model. To determine the importance of each MSA’s feature at the inter-residue level, we added an attention layer to the deep neural network. The model is trained in a multi-task fashion to also predict backbone and orientation angles further improving the inter-residue distance prediction. We show that AttentiveDist outperforms the top methods for contact prediction in the CASP13 structure prediction competition. To aid in structure modeling we also developed two new deep learning-based sidechain center distance and peptide-bond nitrogen-oxygen distance prediction models. Together these led to a 12% increase in TM-score from the best server method in CASP13 for structure prediction.