Protein adsorption on surfaces is used in analytical tools as an immobilization mean to trap the analyte to be detected. However, protein adsorption can lead to a conformational change in the protein structure, resulting in a loss of bioactivity. Here, we study the adsorption of the Streptavidin -Biotin complex on amorphous SiO 2 surfaces functionalized with five different silane selfassembled monolayers by all-atom Molecular Dynamics simulations. We find that the Streptavidin global conformational change increases linearly with the adsorption energy, which depends, as well as the nature of residues with high mobility, on the alkyl chain length and head group charge of silane molecules. Effects on interactions with Biotin are further investigated by Steered Molecular Dynamics (SMD) simulations, which mimics Atomic Force Microscope (AFM) spectroscopy with the Biotin attached on the tip. We show the combined effects of adsorptioninduced global conformational changes and of the position of residues with high mobility on the force of Biotin detachment. By comparing our results to experimental and SMD detachment forces obtained in water, without any surface, we conclude that silane with uncharged and short alkyl chains allow Streptavidin immobilization, with high adsorption energy, while keeping Biotin interactions better than silanes with long alkyl chains or charged head-groups.

Surface chemical functionalization is used in analytical tools to immobilize biomolecules that will capture a specific analyte and also to reduce the nonspecific adsorption. Silane monolayers are widely used to functionalize silica surfaces. Their interfacial properties are linked to the silane organization. Here, we study, by molecular dynamics simulations, the effects of silane molecule headgroup charge, alkyl chain length, and surface coverage on the structure of silane monolayers. Four molecules are investigated: 3aminopropyldimethylethoxysilane, n-propyldimethylmethoxysilane, octadecyldimethylmethoxysilane, and tert-butyl-11-(dimethylamino-(dimethyl)silyl)undecanoate. The results suggest that, while long alkyl chains straighten out and adopt a more organized structure as surface coverage increases, the tilt angle of short chains is independent of surface coverage. Furthermore, in the case of long alkyl chains, a charged head-group seems to reduce the tilt angle to surface coverage dependence. The simulated alkyl chain tilt angles were qualitatively validated by infrared spectroscopy and X-ray photoelectron spectroscopy. Also, a hexagonal packing is observed in all of the monolayers but is more defined as surface coverage increases. The nematic order parameter suggests that this packing is governed by the parallel orientation of the first C−C bonds near the surface. So, even short alkyl chains, with a large tilt angle distribution, present a hexagonal packing.

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In the context of the Covid-19 outbreak since December 2019, antigenic tests are widely used, for diagnosis purpose, to detect the SARS-CoV-2 spike protein in nasopharyngeal fluid through its interactions with specific antibodies. However, the SARS-CoV-2 spike protein is subject to rapid mutations yielding more and more variants which might lose their affinity towards the currently used antibodies. The virus entry into the host cell involves interactions between the Angiotensin-Converting Enzyme 2 and the SARS-CoV-2 spike protein receptor binding domain, which should be preserved whatever the mutations to keep the infectious potential of the virus. However, as the enzyme has not evolved to recognize the virus, its affinity with the spike protein receptor binding domain is lower than with the specific antibodies. The present molecular dynamics simulations study suggests that the adsorption of the Angiotensin-Converting Enzyme 2 on specific silane monolayers could increase its affinity towards the spike protein receptor binding domain. Indeed silane monolayer, combining silane molecules with short alkyl chains and positively charged head-groups and silane molecules without charged head-groups, could adsorb the Angiotensin-Converting Enzyme 2 while keeping its bioactivity (orientation compatible with the spike protein trapping, low conformational changes) and increasing its interactions with the spike protein receptor binding domain (number of hydrogen bonds and electrostatic interactions) to lead to an increase by 20% both in the binding free energy and in the enzyme / receptor binding domain rupture force. This work could help to develop biosensing tools efficient towards any variants of the SARS-CoV-2 spike protein. NH 3 +3-aminopropyldimethylethoxy-silane Mix shortMix CH 3 short: NH 3 + (1:1) Mix longMix CH 3 long: NH 3 + (1:1) MethodsThis work is divided into three parts. Firstly, MD simulations of ACE2 on different types of silane monolayers were performed to select the monolayers that could lead to ACE2 adsorption with an orientation compatible with S-RBD trapping. Also, the adsorption-induced conformational changes in ACE2 were characterized. Secondly, three selected silane monolayers and the complex ACE2 -S-RBD were considered. Adsorption-induced conformational changes in ACE2 were characterized, especially at the interface with S-RBD and compared to the structure of the complex in water without surface. Finally, SMD simulations and Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) analysis gave insight into the impact of conformational changes on the strength of interactions between ACE2 and the S-RBD. System descriptionMD simulations were performed from the PDB crystal structure 6M0J of the ACE2 -S-RBD complex. 15 Water molecules were kept while the zinc and chloride ions were not considered.Regarding the surface, the amorphous SiO 2 layer was taken from Roscioni et al. 21 and resized to the simulation box dimensions with a 2nm-thickness by a home-made Python code. Silane monolayers were built f...