The efficient immobilization of enzymes on surfaces remains a complex but central issue in the biomaterials field (1), which requires us to understand this process at the atomic level. Using a multi-scale approach combining all-atom molecular dynamics and coarse- grain Brownian dynamics simulations, we investigated the adsorption behavior of β-glucosidase A (βGA) on bare and SAM-functionalized gold surfaces (2). 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 (3). 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 (4). References                        1 Hitaishi, V.; Clement, R.; Bourassin, N.; Baaden, M.; de Poulpiquet, A.; Sacquin-Mora, S.; Ciaccafava, A.; Lojou, E., Controlling Redox Enzyme Orientation at Planar Electrodes. Catalysts 2018, 8 (5), 192. 2 Bourassin, N.; Barbault, F.; Baaden, M.; Sacquin-Mora, S., Between two walls : Modeling the adsorption behavior of β-glucosidase on bare and SAM-functionalised gold surfaces, Langmuir 2022, 38, 1313–1323 3 Bourassin, N.; Baaden, M.; Lojou, E.; Sacquin-Mora, S., Implicit Modeling of the Impact of Adsorption on Solid Surfaces for Protein Mechanics and Activity with a Coarse-Grained Representation. J Phys Chem B 2020, 124 (39), 8516-8523. 4 Weltz, J. S.; Kienle, D. F.; Schwartz, D. K.; Kaar, J. L., Reduced Enzyme Dynamics upon Multipoint Covalent Immobilization Leads to Stability-Activity Trade-off. J. Am. Chem. Soc. 2020, 142 (7), 3463-3471.