The SARS-CoV-2 virus causes the coronavirus infection COVID-19 and remains in the focus of the researchers around the world. The penetration of the SARS-CoV-2 virus into the cell begins with the binding of its S-protein to the angiotensin-converting enzyme-2 (ACE2) expressed on the cell surface. The study of the spatial structure of the S-protein is necessary for the understanding of the molecular aspects of its functioning. At present, the structure of almost the entire S-protein molecule has been well studied by experimental methods, with the exception of its endodomain, transmembrane domain, and adjacent ectodomain residues. We performed molecular modeling of the structure of the S-protein fragment corresponding to its supercoiled HR2 domain and fully palmitoylated transmembrane domain. The stability of the model in the lipid bilayer is confirmed by means of molecular dynamics simulations in full-atomic and coarse-grained representation. It was shown that palmitoylation leads to a significant decrease in the mobility of the transmembrane domain and local thickening of the bilayer, which may be important for the process of protein trimerization.

The SARS-CoV-2 virus causes the coronavirus infection COVID-19 and remains in the focus of the researchers around the world. The penetration of the SARS-CoV-2 virus into the cell begins with the binding of its S-protein to the angiotensin-converting enzyme-2 (ACE2) expressed on the cell surface. The study of the spatial structure of the S-protein is necessary for the understanding of the molecular aspects of its functioning. At present, the structure of almost the entire S-protein molecule has been well studied by experimental methods, with the exception of its endodomain, transmembrane domain, and adjacent ectodomain residues. We performed molecular modeling of the structure of the S-protein fragment corresponding to its supercoiled HR2 domain and fully palmitoylated transmembrane domain. The stability of the model in the lipid bilayer is confirmed by means of molecular dynamics simulations in full-atomic and coarse-grained representation. It was shown that palmitoylation leads to a significant decrease in the mobility of the transmembrane domain and local thickening of the bilayer, which may be important for the process of protein trimerization.