Molecular dynamics simulations of the spike protein receptor binding domain adsorption to material surfaces

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Farouq, Mohammed A. Haider and Kubiak-Ossowska, Karina and Al-Qaraghuli, Mohammed M. and Ferro, Valerie A. and Mulheran, Paul A. (2025) Molecular dynamics simulations of the spike protein receptor binding domain adsorption to material surfaces. Journal of Physical Chemistry B, 129 (44). 11421–11429. ISSN 1520-6106 (https://doi.org/10.1021/acs.jpcb.5c04391)

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Abstract

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.

ORCID iDs

Farouq, Mohammed A. Haider, Kubiak-Ossowska, Karina ORCID logoORCID: https://orcid.org/0000-0002-2357-2111, Al-Qaraghuli, Mohammed M. ORCID logoORCID: https://orcid.org/0000-0003-1823-6671, Ferro, Valerie A. ORCID logoORCID: https://orcid.org/0000-0003-1967-3603 and Mulheran, Paul A. ORCID logoORCID: https://orcid.org/0000-0002-9469-8010;
CORE (COnnecting REpositories)