iNucRes-ASSH: Identifying nucleic acid-binding residues in proteins by using self-attention-based structure-sequence hybrid neural network.

Interaction between proteins and nucleic acids is crucial to many cellular activities. Accurately detecting nucleic acid-binding residues (NABRs) in proteins can help researchers better understand the interaction mechanism between proteins and nucleic acids. Structure-based methods can generally make more accurate predictions than sequence-based methods. However, the existing structure-based methods are sensitive to protein conformational changes, causing limited generalizability. More effective and robust approaches should be further explored. In this study, we propose iNucRes-ASSH to identify nucleic acid-binding residues with a self-attention-based structure-sequence hybrid neural network. It improves the generalizability and robustness of NABR prediction from two levels: residue representation and prediction model. Experimental results show that iNucRes-ASSH can predict the nucleic acid-binding residues even when the experimentally validated structures are unavailable and outperforms five competing methods on a recent benchmark dataset and a widely used test dataset.