A Machine Learning Methodology for Enzyme Functional Classification Combining Structural and Protein Sequence Descriptors

Abstract

The massive expansion of the worldwide Protein Data Bank (PDB) provides new opportunities for computational approaches which can learn from available data and extrapolate the knowledge into new coming instances. The aim of this work is to apply machine learning in order to train prediction models using data acquired by costly experimental procedures and perform enzyme functional classification. Enzymes constitute key pharmacological targets and the knowledge on the chemical reactions they catalyze is very important for the development of potent molecular agents that will either suppress or enhance the function of the given enzyme, thus modulating a pathogenicity, an illness or even the phenotype. Classification is performed on two levels: (i) using structural information into a Support Vector Machines (SVM) classifier and (ii) based on amino acid sequence alignment and Nearest Neighbor (NN) classification. The classification accuracy is increased by fusing the two classifiers and reaches 93.4% on a large dataset of 39,251 proteins from the PDB database. The method is very competitive with respect to accuracy of classification into the 6 enzymatic classes, while at the same time its computational cost during prediction is very small.