Effects of different glycosylation motifs on the structural stability and dynamics of the SARS-CoV2 S glycoprotein

Effects of different glycosylation motifs on the structural stability and dynamics of the SARS-CoV2 S glycoprotein is led by Dr Elisa Fadda, Maynooth University, Ireland. Discovering how to regulate activity and pathogenicity of the spike of SARS-Cov-2 is the main task of Dr Fadda's project. The S protein is covered with complex carbohydrates or glycans. These serve as a kind of protection for the virus as it uses them to disguise itself in order to sneak into a human cell unnoticed and deceive the immune system and host cell. With molecular dynamics simulations, however, the game changes. Using this method, scientists can discover this invisible structure of the spike and how it reacts and rearranges when S protein binds with a human cell receptor ACE2. Various cell hosts perform multiple types of glycosylation: the enzymatic process that attaches glycans to proteins. According to the team, this study will indicate if there are different levels of activity of the spike (CoV-2 S glycoproteins), which will be expressed in different cells. Molecular dynamics simulations will provide insight into the functional role of the glycans in the S protein's structure, dynamics, activation, thus discovering its strengths and weaknesses. The goal is to find out how different glycans regulate the spike's activity. Moreover, these crucial vulnerabilities of the spike S could be good targets for specific drugs, effective therapeutic strategies, and diagnostic interventions. The computational resources requested from PRACE will cover the study of five CoV-2 S (spike) models, designed explicitly with different glycosylation at three specific sites. They will be consistent with available data from human cells and with recombinant protein data from collaborators (Dr R.P. De Vries from Utrecht University, The Netherlands). PRACE awarded the project with 15 840 000 core hours on Marconi100, hosted by CINECA, Italy.