(31g) How Confinement and Hydrophobicity Affect CO2 Diffusion from the Bulk Phase to the Active Site of Human Carbonic Anhydrase II: A Study Based on Coarse-Grained Molecular Dynamics Simulation and the Markov-State Model

While nanoconfinement may enhance protein stability and reusability, its impact on the apparent activity of encapsulated enzymes in uncertain due to the complicated interactions among enzyme, substrate and product under confinement. To gain a knowledge for the design, synthesis and application of immobilized enzymes in nanopores, here we applied coarse-grained molecular dynamics simulation (CGMD) and the Markov-state model (MSM) to study CO2 diffusion from the bulk phase to the active site of human carbonic anhydrase II (hCA-II), an enzyme promising for intensified CO2 sequestration. Special efforts were directed at examining the effects of confinement and surface hydrophobicity on hCA-II conformation, orientation and interaction with CO2 molecules. The simulation results show that a hydrophobic pore gives an enhanced local CO2 density near the inner surface, but hinders the diffusion of CO2 from inner surface to active site of hCA-II. A hydrophilic pore hinders the adsorption of CO2 molecules due to the repulsion by the hydrophilic environment. However once CO2 enters the pore the repulsive interaction with the confinement wall would push CO2 toward the encapsulated CA, favouring the transport of CA to the active sites. MSM time-evolved probability analysis shows weak hydrophilic confinement gives the highest active-site-occupied probability. Above results offer a kinetic view with molecular insight and are useful for the design and utilization of encapsulated CA for CO2 sequestration.