HDIContact: a novel predictor of residue–residue contacts on hetero-dimer interfaces via sequential information and transfer learning strategy

Abstract

Abstract Proteins maintain the functional order of cell in life by interacting with other proteins. Determination of protein complex structural information gives biological insights for the research of diseases and drugs. Recently, a breakthrough has been made in protein monomer structure prediction. However, due to the limited number of the known protein structure and homologous sequences of complexes, the prediction of residue–residue contacts on hetero-dimer interfaces is still a challenge. In this study, we have developed a deep learning framework for inferring inter-protein residue contacts from sequential information, called HDIContact. We utilized transfer learning strategy to produce Multiple Sequence Alignment (MSA) two-dimensional (2D) embedding based on patterns of concatenated MSA, which could reduce the influence of noise on MSA caused by mismatched sequences or less homology. For MSA 2D embedding, HDIContact took advantage of Bi-directional Long Short-Term Memory (BiLSTM) with two-channel to capture 2D context of residue pairs. Our comprehensive assessment on the Escherichia coli (E. coli) test dataset showed that HDIContact outperformed other state-of-the-art methods, with top precision of 65.96%, the Area Under the Receiver Operating Characteristic curve (AUROC) of 83.08% and the Area Under the Precision Recall curve (AUPR) of 25.02%. In addition, we analyzed the potential of HDIContact for human–virus protein–protein complexes, by achieving top five precision of 80% on O75475-P04584 related to Human Immunodeficiency Virus. All experiments indicated that our method was a valuable technical tool for predicting inter-protein residue contacts, which would be helpful for understanding protein–protein interaction mechanisms.