Molecular Dynamics Simulations of the Spike Protein Receptor Binding Domain Adsorption to Material Surfaces

The receptor binding domain (RBD) of the SARS-CoV-2 spike
protein
is an important diagnostic and therapeutic target since it binds to
the peptidase domain of the angiotensin-converting enzyme 2 (ACE2)
receptor, thus facilitating infection by the virus. Many diagnostics
utilize the adsorption of proteins onto material surfaces and nanoparticles
to create functional couples. In this work, the adsorption of the
histidine tag (His-Tag) modified RBD on various inorganic surface
models is explored by using fully atomistic molecular dynamics simulations.
The material surfaces used are an experimentally relevant negatively
charged silica surface, a model positively charged surface, and a
self-assembled monolayer terminated with negatively charged carboxyl
groups. The simulations with both negatively charged surface models
show the protein adsorbing rapidly and specifically, while the protein
does not adsorb on the positively charged surface model. Adsorption
of the His-Tag modified RBD on both negative surfaces is also favorable
for device manufacture, with the protein retaining its structure while
its ACE2-binding residues remain free to interact with the environment
due to its orientation in the adsorbed state. Consequently, these
results can guide the development of new diagnostics through the choice
of substrate and protein modification.