Figure 9.

Structure of the TMD of the NMDAR and PES binding. A, B, Side (A) and top (B) view showing the helical organization (M1-M4) of the TMDs and a structural superposition of the unliganded (closed state, filled symbols) model of the GluN1 (gray)/GluN2B (orange) receptor and the liganded (open state, open symbols) model of the receptor from MD simulations (Cerny et al., 2019). C, Interaction of PES (green) with the TMD of GluN1/GluN2B receptor in the closed state obtained by steroid docking followed by a 100-ns-long all-atom MD simulation. Red sticks represent the experimentally identified residues involved in receptor potentiation. Sphere represents the position of the sulfate moiety of PES (green). D, Interaction of PES with the TMD of the GluN1/GluN2B receptor in the open state. E, The model of the TMD of the NMDAR with the ion channel open simulated in the absence of steroid. The GluN2B (M824) residue is in contact with the GluN2B (W559) residue.