Between Two Walls: Modeling the Adsorption Behavior of β-Glucosidase A on Bare and SAM-Functionalized Gold Surfaces

Abstract

The efficient immobilization of enzymes on surfaces remains a complex but central issue in the biomaterials field, which requires us to understand this process at the atomic level. Using a multi-scale approach combining all-atom molecular dynamics and coarsegrain Brownian dynamics simulations, we investigated the adsorption behavior of βglucosidase A (βGA) on bare and SAM-functionalized gold surfaces. We monitored the enzyme position and orientation during the MD trajectories, and measured the contacts it forms with both surfaces. While the adsorption process has little impact on the protein conformation, it can nonetheless perturb its mechanical properties and catalytic activity.Our results show that compared to the SAM-functionalized surface, the adsorption of βGA on bare gold is more stable, but also less specific, and more likely to disrupt the enzyme's function. This observation emphasizes the fact that the structural organization of proteins at the solid interface is a keypoint when designing devices based on enzyme immobilization, as one must find an acceptable stability-activity trade-off.

DockSurf: A Molecular Modeling Software for the Prediction of Protein/Surface Adhesion

“…Our analyses reveal a relatively consistent proportion of residues in contact with the gold surface (approximately 10%) across the three proteins studied. Notably, charged residues such as Glu, Asp, Arg, and Lys show a prevalence in these interactions, consistent with findings from prior studies. ,, …”

“…Over the last years, our team has shown a keen interest to unveil the pivotal role of water at the interface of surfaces such as gold, rutile, quartz, and organic polymers. ,,,, From these studies, it can be drawn that water plays a role in adsorption only at the vicinity of the surface, which can be qualitatively considered through a computation of generalized born solvation . Therefore, to compute quickly the solvent effect, the nine molecules used as templates for protein (cf.…”

“…Notwithstanding its effectiveness, a MD simulation still heavily relies on the protein’s initial orientation and position upon the inorganic surface . To overcome this drawback, a common remedy consists in starting several MD simulations with various initial orientations/positions.…”

DockSurf: A molecular modeling software for the prediction of protein/surface adhesion.

“…Over the last years, our team has shown a keen interest to unveil the pivotal role water at the interface of surfaces such as gold, rutile, quartz and organic polymers 9,21,46,48,49 . From these studies it can be drawn that water plays a role on adsorption only at the vicinity of the surface which can be qualitatively considered through a computation of generalized born solvation 46 .…”

“…Notwithstanding its effectiveness, a MD simulation still heavily relies on the protein's initial orientation and position upon the inorganic surface 21 . To overcome this drawback, a common remedy consists in starting several MD simulations with various initial orientation/position.…”