EnzyNet: enzyme classification using 3D convolutional neural networks on spatial representation

During the past decade, with the significant progress of computational power as well as ever-rising data availability, deep learning techniques became increasingly popular due to their excellent performance on computer vision problems. The size of the Protein Data Bank has increased more than 15 fold since 1999, which enabled the expansion of models that aim at predicting enzymatic function via their amino acid composition. Amino acid sequence however is less conserved in nature than protein structure and therefore considered a less reliable predictor of protein function. This paper presents EnzyNet, a novel 3D-convolutional neural networks classifier that predicts the Enzyme Commission number of enzymes based only on their voxel-based spatial structure. The spatial distribution of biochemical properties was also examined as complementary information. The 2-layer architecture was investigated on a large dataset of 63,558 enzymes from the Protein Data Bank and achieved an accuracy of 78.4% by exploiting only the binary representation of the protein shape. Code and datasets are available at https://github.com/shervinea/enzynet.Comment: 11 pages, 6 figure

Automatic single- and multi-label enzymatic function prediction by machine learning

The number of protein structures in the PDB database has been increasing more than 15-fold since 1999. The creation of computational models predicting enzymatic function is of major importance since such models provide the means to better understand the behavior of newly discovered enzymes when catalyzing chemical reactions. Until now, single-label classification has been widely performed for predicting enzymatic function limiting the application to enzymes performing unique reactions and introducing errors when multi-functional enzymes are examined. Indeed, some enzymes may be performing different reactions and can hence be directly associated with multiple enzymatic functions. In the present work, we propose a multi-label enzymatic function classification scheme that combines structural and amino acid sequence information. We investigate two fusion approaches (in the feature level and decision level) and assess the methodology for general enzymatic function prediction indicated by the first digit of the enzyme commission (EC) code (six main classes) on 40,034 enzymes from the PDB database. The proposed single-label and multi-label models predict correctly the actual functional activities in 97.8% and 95.5% (based on Hamming-loss) of the cases, respectively. Also the multi-label model predicts all possible enzymatic reactions in 85.4% of the multi-labeled enzymes when the number of reactions is unknown. Code and datasets are available at https://figshare.com/s/a63e0bafa9b71fc7cbd7