Improved protein structure prediction by deep learning irrespective of co-evolution information

Predicting the tertiary structure of a protein from its primary sequence has been greatly improved by integrating deep learning and co-evolutionary analysis, as shown in CASP13 and CASP14. We describe our latest study of this idea, analysing the efficacy of network size and co-evolution data and its performance on both natural and designed proteins. We show that a large ResNet (convolutional residual neural networks) can predict structures of correct folds for 26 out of 32 CASP13 free-modelling targets and L/5 long-range contacts with precision over 80%. When co-evolution is not used, ResNet can still predict structures of correct folds for 18 CASP13 free-modelling targets, greatly exceeding previous methods that do not use co-evolution either. Even with only the primary sequence, ResNet can predict the structures of correct folds for all tested human-designed proteins. In addition, ResNet may fare better for the designed proteins when trained without co-evolution than with co-evolution. These results suggest that ResNet does not simply de-noise co-evolution signals, but instead may learn important protein sequence-structure relationships. This has important implications for protein design and engineering, especially when co-evolutionary data are unavailable. In the last few years, computational protein structure prediction has greatly advanced by combining deep learning including convolutional residual networks (ResNet) with co-evolution data. A new study finds that using deeper and wider ResNets improves predictions in the absence of co-evolution information, suggesting that the ResNets do not not simply de-noise co-evolution signals, but instead may learn important protein sequence-structure relationships.

Automated summary

Recent advances in computational protein structure prediction have shown significant improvements by integrating deep learning and co-evolutionary analysis. Using ResNet, predictions of correct protein folds have been successful even without co-evolution information, suggesting potential for learning important protein sequence-structure relationships.