Extended Data Fig. 10: Hydrogen-bond network in the Asn ring and extent of hydrophobic interactions.

a,b, Probability density distributions (100 bins) of h-bond distances between all feasible pairs of hydrogen bond doner and acceptor moieties in the Asn ring for the agonist-bound (panel a) and agonist-memantine-bound (panel b) structures. Density distributions for GluN2B-Asn615 (chain B and D) are in green and red. Those for GluN1a-Asn616 (chain A)/GluN2B-Asn615 (chain B and D) and GluN1a-Asn616 (chain C)/GluN2B-Asn615 (chain B and D) are in yellow and blue, respectively. Asterisks denote the interaction pairs for which h-bonds are the main interaction, as suggested by the highest peak at ~2.5 Å. The structures are representative snapshots of collective variables that maximize the total number of possible simultaneous h-bonding interactions. The Asn rings are viewed from the extracellular space where representative h-bonds are depicted as dashed yellow lines. The nitrogen atom h-bond doner variable is represented as the COG between both N⁺-H atoms. Note that the h-bond network patterns for (S)-(+)-ketamine and PCP are similar to the agonist-bound structure. c, Comparison of binding of PCP pose-1 (orange sticks), memantine (gray sticks), and S-(+)-ketamine pose-2, 3, and 4 (cyan sticks) showing inter-carbon (C-C) interactions within 5 Å (yellow dots) and a hydrogen bond (green dots, arrow).