Tandem bio-catalysis is able to fully utilize the bond energy stored in complex molecule by using sequential active sites. This results in an enhanced efficiency in electrocatalytic devices, enabling biofuel cells with higher energy density and biosensors with high sensitivity. Mass transport of reaction intermediate molecules is a key factor impacting the overall kinetics, which in nature is facilitated by substrate channeling, where intermediates are directly shuttled to the next active site instead of diffusing into the bulk.¹

Electrostatic channeling represents one such mechanism, where charged intermediates are transported along an oppositely charged pathway. Natural electrostatic cascades have been studied for decades, and in 2017 we reported the first cascade with artificially introduced electrostatic channeling.² This finding highlighted a surface diffusion mechanism on a 1D channeling bridge. However, intermediate transport between the bridge and the downstream enzyme binding site occurs on a flexible 2D surface exhibiting a range of interactions with the intermediate and potentially greater leakage. This process is of great significance to further explore the channeling kinetics and also make optimization for cascade design. Here, we are going to further map the channeling pathway between the bridge and intermediate active site. Enhanced sampling methods is used to elucidate the intermediate’s ergodicity in this process. Finally, kinetic Monte Carlo method is used to quantify the overall kinetics, from which the leaking contribution from each channeling region can be evaluated.

REFERENCE

1. I. Wheeldon, S. D. Minteer, S. Banta, S. C. Barton, P. Atanassov and M. Sigman, "Substrate channelling as an approach to cascade reactions", Nature Chemistry, 8, 299–309 (2016). doi:10.1038/nchem.2459.
2. Y. Liu, D. P. Hickey, J.-Y. Guo, E. Earl, S. Abdellaoui, R. D. Milton, M. S. Sigman, S. D. Minteer and S. Calabrese Barton, "Substrate Channeling in an Artificial Metabolon: A Molecular Dynamics Blueprint for an Experimental Peptide Bridge", ACS Catalysis, 7, 2486–2493 (2017). doi:10.1021/acscatal.6b03440.