CopulaNet: Learning residue co-evolution directly from multiple sequence alignment for protein structure prediction

• Published in: Nature communications 2021-05, Vol.12 (1), p.2535-2535, Article 2535
• Main Authors: Ju, Fusong, Zhu, Jianwei, Shao, Bin, Kong, Lupeng, Liu, Tie-Yan, Zheng, Wei-Mou, Bu, Dongbo
• Format: Article
• Language: English
• Subjects: 631/114/1305; 631/114/2411; Alignment; Amino acid sequence; Artificial neural networks; Caspases - chemistry; Coders; Coevolution; Computational Biology; Covariance matrix; Deep learning; Evolution; Humanities and Social Sciences; Humans; Machine Learning; Models, Molecular; multidisciplinary; Mutation; Neural networks; Neural Networks, Computer; Nucleotide sequence; Predictions; Protein structure; Protein Structure, Tertiary; Proteins; Proteins - chemistry; Proteins - genetics; Residues; Science; Science (multidisciplinary); Sequence Alignment
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-22869-8

Residue co-evolution has become the primary principle for estimating inter-residue distances of a protein, which are crucially important for predicting protein structure. Most existing approaches adopt an indirect strategy, i.e., inferring residue co-evolution based on some hand-crafted features, say, a covariance matrix, calculated from multiple sequence alignment (MSA) of target protein. This indirect strategy, however, cannot fully exploit the information carried by MSA. Here, we report an end-to-end deep neural network, CopulaNet, to estimate residue co-evolution directly from MSA. The key elements of CopulaNet include: (i) an encoder to model context-specific mutation for each residue; (ii) an aggregator to model residue co-evolution, and thereafter estimate inter-residue distances. Using CASP13 (the 13th Critical Assessment of Protein Structure Prediction) target proteins as representatives, we demonstrate that CopulaNet can predict protein structure with improved accuracy and efficiency. This study represents a step toward improved end-to-end prediction of inter-residue distances and protein tertiary structures. Protein structure prediction is a challenge. A new deep learning framework, CopulaNet, is a major step forward toward end-to-end prediction of inter-residue distances and protein tertiary structures with improved accuracy and efficiency.