Kinetic Monte Carlo Simulation of Substrate Channeling Via Electrostatic Interactions

Abstract

Multistep electrocatalytic cascades are capable of expanding the range and extent of electrochemical reactions, leading to fuel cells with high energy density and sensors with enhanced sensitivity[1]. In such processes, a key limitation is the mass transport of reaction intermediate between spatially organized active sites. Substrate channeling, by which reaction intermediates are directly transported to downstream active sites without equilibrating to the bulk environment, is a key aspect of efficient cascades[2]. However, the application to artificial systems is hindered by the need for molecular-level design and experiments often on nanosecond time scales. Multiscale simulation of multistep cascades bridges the gap between molecular interaction and experiment results. Channeling via surface interactions involves simultaneously occurring reaction, adsorption, desorption, surface diffusion and bulk diffusion. Kinetic Monte Carlo (KMC) method is widely used to characterize the overall kinetics of heterogeneous catalysis with complex and coupled events[3]. Here, we describe the use of KMC simulation, aided with Molecular Dynamics (MD), to study the channeling in an enzymatic complex system with electrostatic bridge, aiming to quantify the overall kinetics, identify the potential limitation step, and bridge the gap between molecular simulation and experiment result (e.g., stop-flow lag time experiment). In this project, we proposed a channeling model with discrete reaction and hopping sites, as shown in Fig. 1a. Events on each individual site is allowed to interact with the external environment (e.g., bulk intermediate concentration). For rate-limiting enzyme kinetics, Fig. 1c shows an example of lag time, an experimentally accessible metric, on channeling efficiency. Specifically, when the desorption rate for intermediate on E2 is low (k2 = 0.1 kcat), the lag time significantly decreases (from 212 s to 19 s) with improved substrate channeling. However, Fig. 1e shows that the bridge has minimal impact when the desorption rates on E2 represents typical enzyme systems (k2 = 10 kcat). This indicates that in an ideal channeling system, the functional bridge should be able to protect the adsorbed intermediate from equilibrating to bulk environment[4,5]. In addition, if the bulk intermediate is allow to re-adsorb onto the bridge, the bridge impact saw a great increase (Fig.1e) in spite of high k2 value. Therefore, the behavior of intermediate molecules around bridge/enzyme boundary is of great significance. Based on these results, we are able to identify the potential limiting factors on overall kinetics, which highlights the primary interactions to be studied by integrated molecular simulation and experiment. Acknowledgement We gratefully acknowledge support from Army Research Office MURI (#W911NF1410263) via The University of Utah