ABSTRACT
SARS-CoV-2, the causative agent of COVID-19, remains the focus of research worldwide. SARS-CoV-2 entry into the cell starts with its S protein binding to the angiotensin-converting enzyme-2 (ACE2) expressed on the cell surface. The knowledge of the S protein's spatial structure is indispensable for understanding the molecular principles of its work. The S protein structure has been almost fully described using experimental approaches with the only exception for the protein's endodomain, the transmembrane domain, and the ectodomain parts adjacent to the latter. The paper reports molecular modelling of the S protein fragment corresponding to its coiled coil HR2 domain and fully palmitoylated transmembrane domain. Model stability in lipid bilayer was confirmed by all-atom and coarse-grained molecular dynamics simulations. It has been demonstrated that palmitoylation leads to a significant decrease in transmembrane domain mobility and local bilayer thickening, which may be relevant for protein trimerization.
ABSTRACT
Antiseptics are an essential line of defense against bacterial and viral infections in modern medical practice. Many of them are supposed to act on microbial membranes. However, the detailed mechanisms of their action are still elusive. Here, we utilized coarse-grained molecular dynamics simulations to investigate interactions of different types of cationic antiseptics (CAs) with a model bacterial membrane. The simulations revealed qualitatively distinct patterns of dynamic and structural alterations of membrane induced by different types of antiseptics although none of them caused disintegration or solubilization of the bilayer even at the highest explored concentration. At the same time, the adsorption of antiseptics rendered membranes more vulnerable to poration under exposure to the external electric field. We further discuss the possible relation of the enhanced pore formation induced by CAs to their cytotoxic action.
