Simulation Study of Carbonic Anhydrase Adsorption on Self-Assembled Monolayers

Carbonic anhydrase (CA) is a zinc-containing metalloenzyme that can rapidly catalyze the interconversion of CO₂ and bicarbonate under suitable conditions. In industrial applications such as carbon capture, the performance of immobilized CA is highly related to its adsorption orientation and conformational changes on different carrier surfaces. In this work, the combined simulations of Parallel Tempering Monte Carlo and all-atom molecular dynamics were employed to uncover the adsorption mechanisms, orientations, and conformational changes of CA on charged self-assembled monolayers with different surface charge densities. The simulation results demonstrate that the adsorption of CA on charged surfaces is dominated by electrostatic interactions and influenced by the distribution of charged areas on the surface. CA adsorbs on the NH₂-SAM surfaces with a ″bottom-on″ orientation with its active pocket facing the solution, which is beneficial for the catalytic process of CA. Asp160 was identified as a common adsorption residue for CA on NH₂-SAM surfaces with different SCDs. Furthermore, the native structure of CA is well preserved after adsorption on the NH₂-SAM surface, which is advantageous for the recovery of the catalytic activity of immobilized CA. In summary, this work elucidates the role of surface charge in regulating the adsorption orientation of carbonic anhydrase and its conformational changes during the adsorption process at the molecular level and provides theoretical guidance for the design of CA-based biocatalysts.