Alignment-Free Method to Predict Enzyme Classes and Subclasses

Riccardo Concu,M Natália D S Cordeiro

doi:10.3390/ijms20215389

Riccardo Concu, M Natália D S Cordeiro

Open Access

https://doi.org/10.3390/ijms20215389

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Abstract

The Enzyme Classification (EC) number is a numerical classification scheme for enzymes, established using the chemical reactions they catalyze. This classification is based on the recommendation of the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology. Six enzyme classes were recognised in the first Enzyme Classification and Nomenclature List, reported by the International Union of Biochemistry in 1961. However, a new enzyme group was recently added as the six existing EC classes could not describe enzymes involved in the movement of ions or molecules across membranes. Such enzymes are now classified in the new EC class of translocases (EC 7). Several computational methods have been developed in order to predict the EC number. However, due to this new change, all such methods are now outdated and need updating. In this work, we developed a new multi-task quantitative structure–activity relationship (QSAR) method aimed at predicting all 7 EC classes and subclasses. In so doing, we developed an alignment-free model based on artificial neural networks that proved to be very successful.

Highlights

By the late 1950s, the International Union of Biochemistry and Molecular Biology foresaw the need for unique nomenclature for enzymes
We used the linear discriminant analysis (LDA) algorithm implemented in the software STATISTICA® [40] to derive a linear model able to discriminate all of the subclasses of enzymes using a multi-task model, which means that a single model was developed in order to assign each enzyme to a specific class
In the case of the artificial neural networks (ANNs) model, we identified that the same four variables used in the LDA model were able to perfectly discriminate between enzymes and non-enzymes and assign each enzyme sequence to a specific subclass

Summary

Introduction

By the late 1950s, the International Union of Biochemistry and Molecular Biology foresaw the need for unique nomenclature for enzymes. In 1961, the IUB released the first version of the Enzyme Classification (EC) and Nomenclature List This nomenclature was based on assigning a four number code to enzymes with the following meaning: (i) the first number identifies the main enzyme class; (ii) the second digit indicates the subclass; (iii) the third number denotes the sub-subclass; and (iv) the fourth digit is the serial number of the enzyme in its sub-subclass. In August 2018, a new class was added This new class contains the translocases (EC 7), and was added to describe those enzymes catalyzing the movement of ions or molecules across membranes or their separation within membranes. For this reason, some enzymes which had previously been classified in other classes—EC 3.6.3 for example—were included in the EC 7 class

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