Multiscale Modelling of the Electrocatalysis of Microenzymes: Insights Into the Performance of Microperoxidase at an Aqueous/Graphene Interface and Their Exploitation to Improve Performance

ABSTRACT There is great interest in systems where enzymes are adsorbed on and act at electrode surfaces, including enzymatic biofuel cells, bioreactors, and biosensors. Although studied extensively since the 1960s, progress is hindered by a lack of molecular‐level understanding of enzyme adsorption and the associated electron transfer processes. Herein, we present a multiscale approach combining molecular dynamics (MD) simulation to elucidate the former and density functional theory (DFT) for the latter. The demonstration focuses on a system involving microperoxidase‐11 (MP‐11), a microenzyme made up of a Fe‐containing heme ring attached to an 11‐residue scaffold, a graphene electrode, and a neutral‐pH saline solution. Adsorbed MP‐11 was found to adopt six possible heme configurations, defined by the iron‐to‐graphene distance and the angle between the heme and graphene normals. The electron transfer rate constants, evaluated by combining MD and DFT results, and their variation with overpotential are comparable to the limited experimental data. The results also illustrate how the new multiscale approach can suggest experimental strategies, from targeted protein engineering to changes in substrate conditions, for improving the electrocatalytic performance of MP‐11/graphene and, more broadly, of other microenzyme/electrode systems of interest across bioelectrocatalysis, biosensing, and bioenergy.