Generation and Computational Characterization of a Complex Staphylococcus aureus Lipid Bilayer

Studies indicate a crucial cell membrane role in the antibiotic resistance of Staphylococcus aureus. To simulate its membrane structure and dynamics, a complex molecular-scale computational representation of the S. aureus lipid bilayer was developed. Phospholipid types and their amounts were optimized by reverse Monte Carlo to represent characterization data from the literature, leading to 19 different phospholipid types that combine three headgroups [phosphatidylglycerol, lysyl-phosphatidylglycerol (LPG), and cardiolipin] and 10 tails, including iso- and anteiso-branched saturated chains. The averaged lipid bilayer thickness was 36.7 Å, and area per headgroup was 67.8 Å2. Phosphorus and nitrogen density profiles showed that LPG headgroups tended to be bent and oriented more parallel to the bilayer plane. The water density profile showed that small amounts reached the membrane center. Carbon density profiles indicated hydrophobic interactions for all lipids in the middle of the bilayer. Bond vector order parameters along each tail demonstrated different C–H ordering even within distinct lipids of the same type; however, all tails followed similar trends in average order parameter. These complex simulations further revealed bilayer insights beyond those attainable with monodisperse, unbranched lipids. Longer tails often extended into the opposite leaflet. Carbon at and beyond a branch showed significantly decreased ordering compared to carbon in unbranched tails; this feature arose in every branched lipid. Diverse tail lengths distributed these disordered methyl groups throughout the middle third of the bilayer. Distributions in mobility and ordering reveal diverse properties that cannot be obtained with monodisperse lipids.