Implicit Modeling of the Impact of Adsorption on Solid Surfaces for Protein Mechanics and Activity with a Coarse-Grained Representation

Abstract

Surface immobilized enzymes play a key role in numerous biotechnological applications such as biosensors, biofuel cells or biocatalytic synthesis. As a consequence, the impact of adsorption on the enzyme structure, dynamics and function needs to be understood on the molecular level as it is critical for the improvement of these technologies. With this perspective in mind, we used a theoretical approach for investigating local protein flexibility on the residue scale that couples a simplified protein representation with an elastic network and Brownian Dynamics simulations. The impact of protein adsorption on a solid surface is implicitly modeled via additional external constraints between the residues in contact with the surface. We first performed calculations on a redox enzyme, bilirubin oxidase (BOD) from M. verrucaria, to study the impact of adsorption on its mechanical properties. The resulting rigidity profiles show that, in agreement with the available experimental data, the mechanical variations observed in the adsorbed BOD will depend on its orientation and its anchor residues (i.e. residues that are in contact with the functionalized surface). Additional calculations on ribonuclease A and nitroreductase shed light on how seemingly stable adsorbed enzymes can nonetheless display an important decrease in their catalytic activity resulting from a perturbation of their mechanics and internal dynamics.

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

“…16 This can be achieved either through targeted chemical linkage between the protein and the surface, [17][18][19] or via the adequate functionalization of the surface, for exemple with self-assembled monolayer (SAMs), in order to adapt its charge and physico-chemical properties to a specific protein. [20][21][22][23] One must also pay attention to the conservation of the adsorbed protein's structure and dynamics, as perturbations in the protein conformation [24][25][26] or internal mobility 27 are likely to result in a dramatic decrease of the catalytic activity.…”

From Enzyme Stability to Enzymatic Bioelectrode Stabilization Processes

“…Microscopy coupled to electrochemistry will allow the mapping of the electrocatalysis [318][319][320]. Finally, getting more and more accurate experimental data on enzyme behavior on electrodes may be implemented in theoretical models that in return will help in bioelectrode rationalization [21,117,[321][322][323].…”

“…In the case of immobilized enzyme, it was expected that only the amino acids on the surface of the enzyme will sense the support. However, by looking at the rigidity profile obtained by Brownian dynamics simulations, it was very recently shown that even amino acids in the core of the enzyme can be affected depending on the surface charge of the support [117].…”

Toward the Specificity of Bare Nanomaterial Surfaces for Protein Corona Formation

“…In this view, specific surface topographies and surface modifiers would determine protein coronas with selected compositions [ 147 ]. Regarding protein orientation and structural evolution upon corona formation, Bourassin and colleagues proposed a coarse-grained, elastic network representation to implicitly model the impact of surface adsorption on protein mechanics [ 148 ]. However, to obtain design rules for proteins and surfaces with determined binding characteristics, researchers often oversimplify the interaction mechanisms, focusing on only one or a few of the properties influencing the affinity or the specificity of the proteins for the surfaces.…”