Redox enzymes have been extensively exploited as electrocatalysts in biofuel cells and biosensors due to the advantages they have over commonly used inorganic catalysts. For example, they often have higher activity and selectivity than the inorganic catalysts and can operate at biologically benign conditions. However, additional improvements have to be made for the development of enzymatic electrodes with high activity, stability, and ease of production that can lead to broader applications of enzyme-based systems. Immobilization and optimal interaction of the proteins with the support material is one of the key components in the design of enzymatic electrodes. Therefore, rational design of the electrode surface provides one of the most promising routes for creating biofuel cells and biosensors with enhanced performances. Such a design, however, demands deeper understanding of the bio-nano interface interactions as well as efficient enzyme orientation, which can be achieved by the use of various computational approaches. 

Density Functional Theory (DFT) and docking simulations were used to gain a fundamental understanding of the role of different molecules explored as orienting and/or mediating agents in the design and operation of several enzymatic electrodes. Different computational approaches were first used to explain the role of 1,2-benzoquinone, 1,4-benzoquinone, and ubiquinone on the operation and mechanism of electron transfer in PQQ-dependent soluble glucose dehydrogenase anodes (1, 2).  The same approach was also used to understand the role of bilirubin in the bilirubin-modified oxygen reducing bio-cathodes based on bilirubin oxidase. We further studied the interaction of unsubstituted phenothiazine with glucose, lactate and cholesterol oxidases. Namely, it has been shown that the hydrophobic phenothiazine can be utilized for efficient electron transfer in various oxidases. In addition, docking simulations were used to discuss the nature of the interactions between flavins and outer membrane cytochromes of Shewanella spp., which has practical implication in the development of microbial fuel cells.

1.         Babanova S, Matanovic I, Atanassov P. Quinone-modified surfaces for enhanced enzyme-electrode interactions in PQQ-dependent glucose dehydrogenase anodes. Chem Electro Chem. 2014;1(11):2017–28.

2.         Babanova S, Matanovic I, Chavez MS, Atanassov P. The role of quinones in electron transfer of PQQ-glucose de-hydrogenase anodes – mediation or orientation effect. J. Am. Chem. Soc. 2015;137(24):7754-7762.