Simulation of fully glycosylated EGFR.

<p>(A) A fully glycosylated ectodomain dimer of EGFR. The BiS1F1, Man8, and Man6 glycans attached to EGFR are colored by atom type (gray for carbon, red for oxygen, and blue for nitrogen). (B) The conformation at the end of the simulation shown from two opposite directions. (C) Distance between the N terminus of each ligand (blue, membrane-facing ligand; red, solvent-facing ligand) and the membrane surface (see <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003742#s4" target="_blank">Methods</a>) in the glycosylated-EGFR simulation, and total surface area of the ligand buried due to its interactions with the receptor and the membrane (left panels). Also shown are the results of the MM/GBVI calculations of the free energy of each ligand's interaction with its host receptor in the glycosylated two-ligand EGFR dimer (middle panel) and the results of similar calculations for each ligand's interaction with the membrane bilayer (the right panel). The membrane-facing ligand enjoys greater binding free energy, and thus higher binding affinity, than the solvent-facing one due to the additional energy conferred by the membrane interaction.