(416c) Comprehensive Computational Study of the Realistic, Complex, and Multicomponent Lipid Bilayer of Staphylococcus Aureus

Lipid bilayer compositions of bacteria such as Staphylococcus aureus have a crucial role in their resistance against different antimicrobial drugs. Hence, obtaining physical insights into the structure and dynamics of lipids would contribute to the design of better antimicrobial drugs. Typical idealized models cannot represent the dynamics, compressibility, and interfacial interactions of real bacterial membranes. In this study, we modeled a multicomponent lipid bilayer of Staphylococcus aureus with various leaflets. 19 different lipid types were employed by implementing the reverse Monte Carlo technique using experimental data. They used a combination of three head groups [phosphatidylglycerol (PG), Lysyl-PG (L-PG), and cardiolipin (CL)], three types of fatty acid tail [branched (anteiso and iso), saturated, and unsaturated], and a chain length range of 15-20. The current CHARMM36 library was used to develop the force field parameters of these lipids. The NAMD package was used for Molecular Dynamics (MD) simulations. MD simulations of 60.5 ns equilibration followed by 600 ns of sampling were conducted on this system to calculate static and dynamic membrane characteristics. Density profiles of different atoms show leaflets overlap by ±10 Å, which indicates high hydrophobic tail-tail interactions at the center of the lipid bilayer for all lipid types. On the basis of C-H order parameter calculations, methyl branches increased the fluidity of C-H motions near the center of the Staphylococcus aureus membranes compared to bilayers with linear saturated phospholipids. In addition, to study the fluidity within each leaflet, the time autocorrelation function of the vector between phosphorus and the carbon atom at the end of the tails was calculated for all lipids. Results demonstrated that even lipids of the same type have different relaxation rates. Voronoi tessellation was used in 3D space to determine the volume of each lipid and the area per head group of each lipid at the water-membrane interface region. Within the interface, lipid and water molecules occupied similar extents of area. Self-diffusion coefficient of each lipid was calculated using mean-squared displacements of phosphorous atoms. The diffusion coefficient was in the range of 3-6×10^-8 cm²/s and was slightly higher for PG lipids compared to the L-PG lipids. Studying this complex lipid bilayer system led us to biophysical insights that cannot be achieved by applying simple idealized models.