Fig. 4

MD simulations reveal that PE–protein interactions perturb the charge-relay networks. MD simulations predict specific interactions between the PE headgroup and charged residues of networks 1 and 2 in XylE. a Simulation box. Representative snapshot of XylE (PDB: 4JA4) embedded in an explicit lipid bilayer and water box with 100  mM NaCl. Lipid molecules are shown in line representation colored in silver, phosphorus atom of the headgroup represented by orange spheres. Yellow and green spheres represent Na ⁺ and Cl^- ions, respectively. b Representative snapshot of the close-up of network 1 interacting with the PE headgroup of the phospholipid. Polar interactions with R84 and E153 prevent network formation and steric hindrance prevents contacts of the TM2 and TM11. c Location of the phosphorus atoms of the PE/PC lipid molecule in two 500  ns trajectories in PE:PG:CL bilayers (left) and PC:PG:CL bilayers (right). The spheres are color coded: red at t  =  0  ns and blue at t  =  500  ns. In both simulations 1 and 2, PE lipids wedge between the helices (more so in simulation 1), but no lipid–protein interaction is observed in PC bilayers. In simulation 1, direct interactions with residues R84, E153 and R404 of network 1 are observed