Extended Data Fig. 5: An embedded POPG helps stabilize charged residues within the binding pocket during molecular dynamics simulations.
From: An embedded lipid in the multidrug transporter LmrP suggests a mechanism for polyspecificity
a, Minimum distance between D142 (atoms Oδ1, Oδ2) and K357 (atom Nz). The plot compares the value of this distance in the crystal structure (horizontal gray dashed line) with time-averages calculated from the final 100 ns of the simulations of LmrP-Hoechst and those of LmrP-Hoechst-POPG. Error bars denote the standard deviations of the time-averages. b, 3D mass-density maps of D142 and K357 from simulations with only Hoechst 33342 (magenta), and from simulations with Hoechst 33342 and POPG (teal) highlight the difference in position of D142 in the absence of POPG. The conformations of D142 and K357 at the end of each simulation are shown as a visual aid. c) In simulations with POPG present (teal and cyan) the distance between R14 and D142 is consistent with that observed in the crystal structure. When POPE is modeled instead of POPG (light orange and dark orange), the R14-D142 salt bridge breaks off, as observed when no lipid is modeled (Fig. 3d), but in the simulated timescale R14 remains within the binding cavity. Two independent trajectories for each simulation condition are shown. Source data are available online.
