Scientific Reports volume 10, Article number: 13351 (2020) Cite this article

Author Summary Protein contact prediction and contact-assisted folding has made good progress due to direct evolutionary coupling analysis (DCA). However, DCA is effective on only some proteins with a very large number of sequence homologs. To further improve contact prediction, we borrow ideas from deep learning, which has recently revolutionized object recognition, speech recognition and the GO game. Our deep learning method can model complex sequence-structure relationship and high-order correlation (i.e., contact occurrence patterns) and thus, improve contact prediction accuracy greatly. Our test results show that our method greatly outperforms the state-of-the-art methods regardless how many sequence homologs are available for a protein in question. Ab initio folding guided by our predicted contacts may fold many more test proteins than the other contact predictors. Our contact-assisted 3D models also have much better quality than homology models built from the training proteins, especially for membrane…