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Identifying the Enzymatic Mode of Action for Cellulase Enzymes by Means of Docking Calculations and a Machine Learning Algorithm

1 Department of Chemical and Biological Engineering, Colorado School of Mines, Golden, CO 80401, USA;
2 Department of Electrical Engineering and Computer Science, Colorado School of Mines, Golden, CO 80401, USA

Docking calculations have been conducted on 36 cellulase enzymes and the results were evaluated by a machine learning algorithm to determine the nature of the enzyme (i.e. endo- or exo- enzymatic activity). The docking calculations have also been used to identify crucial substrate-enzyme interactions, and establish structure-function relationships. The use of carboxymethyl cellulose as a docking substrate is found to correctly identify the endo- or exo- behavior of cellulase enzymes with 92% accuracy while cellobiose docking calculations resulted in an 86% predictive accuracy. The binding distributions for cellobiose have been classified into two distinct types; distributions with a single maximum or distributions with a bi-modal structure. It is found that the uni-modal distributions correspond to exo- type enzyme while a bi-modal substrate docking distribution corresponds to endo- type enzyme. These results indicate that the use of docking calculations and machine learning algorithms are a fast and computationally inexpensive method for predicting if a cellulase enzyme possesses primarily endo- or exo- type behavior, while also revealing critical enzyme-substrate interactions.
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Keywords Carboxymethyl cellulose; Cellobiohydrolase; Cellobiose; Cellulase; Docking; Endoglucanase; Machine learning; Product inhibition

Citation: Somisetti V. Sambasivarao, David M. Granum, Hua Wang, C. Mark Maupin. Identifying the Enzymatic Mode of Action for Cellulase Enzymes by Means of Docking Calculations and a Machine Learning Algorithm. AIMS Molecular Science, 2014, 1(1): 59-80. doi: 10.3934/molsci.2014.1.59


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