Unraveling the orientation of an enzyme adsorbed onto a metal–organic framework

Bio-conversion of lignocellulosic biomass to bioethanol fuel is a highly desirable yet challenging objective because of the low catalytic activity and high cost of β-glucosidase (BGL). Recently, ZIF-8, an emerging organic porous material, has been proposed as a promising candidate for enzyme immobilization to improve associated activity and stability. However, the underlying interaction mechanism of binding BGL on the ZIF-8 surface is yet to be clarified. Here, the adsorption of BGL onto ZIF-8 is explored for the first time by molecular dynamics simulations. The results show that BGL adsorbs on the ZIF-8 surface with a "back-on" orientation. The adsorption free energy analysis shows that the adsorption process is enthalpy driven. In addition, the electrostatic interaction between negatively charged residues and Zn²⁺ on the surface of ZIF-8 is found to play a decisive role in surface binding, which accounts for 98% of the total interaction energy. The secondary structure of BGL is not affected despite the strong adsorption, suggesting the good biocompatibility of ZIF-8. This study not only provides a reliable theoretical insight into understanding the interaction mechanism between BGL and ZIF-8, but also helps the rational design of ZIF-8-based materials for bio-related applications.