(A) Overview of the PSA workflow for quantifying similarity between D-serine binding pathways. (B) 2-dimensional order parameter () that describes the degree of GluN2A LBD closure. For each of the …
Simulation summary: overview of simulation systems.
Record of all successful binding pathways in each simulation system for D-serine binding to GluN2A.
Per-residue contact frequency analysis for D-serine binding to GluN2A by cluster identified with PSA.
GluN2A residues most frequently contacted by D-serine given that the pathway results in successful binding – listed for each simulation system.
(A) 2-dimensional order parameter () that describes the degree of GluN1 LBD closure. For each of the above (B–E), the left image shows D-serine density, while the right image shows the residues …
Record of all successful binding pathways in each simulation system for D-serine binding to GluN1.
Per residue contact frequency analysis for D-serine binding to GluN1 by cluster identified with PSA.
GluN1 residues most frequently contacted by D-serine given that the pathway results in successful binding – listed for each simulation system.
Umbrella sampling molecular dynamics simulations were used to compute the potential of mean force (PMF) along the () order parameter for (A) D-serine bound to GluN2A, (B) glycine bound to GluN2A, …
Per-residue contact frequency analysis of the bound state for each agonist computed from lowest-energy conformers extracted from umbrella sampling simulations.
(A) Binding-site residues for D-serine bound to the GluN2A LBD computed from lowest-energy conformers (1 kcal mol–1) from umbrella sampling simulations. Residues with >50% contact frequency in the …
The colors of the colorbar correspond to the standard deviation in kcal mol–1, which was computed for each window over 10 blocks.
(A) Representative Two-electrode voltage clamp (TEVC) recording on GluN1/GluN2A NMDARs expressing oocytes. The traces show inhibition of the NMDAR current by the GluN1 agonists D-serine (left) and …
(A) Overlay of D-serine (teal) and glutamate (gray) density. (B) Residues that distinguish D-serine (teal) from glutamate (gray) binding pathways (see Figure 5—source data 2).
Record of all successful binding pathways in each simulation system for glutamate binding to GluN2A.
Comparison of relative residue contact frequency for D-serine and glutamate.
N-linked Man5GlcNAc2 (Man5) glycans (A) N443-Man5 and N444-Man5 for GluN2A and (B) N491-Man5 for GluN1. Glycan conformational energy landscapes for (C) GluN2A N443-Man5, (D) GluN2A N444-Man5, and (E)…
Comparison of relative residue contact frequency during GluN2A and GluN1 binding pathways for glycosylated and non-glycosylated simulations.
(A) Schematic of the Man5 glycan. (B) Contact network involving the GluN2A N443-Man5 glycan and residues Glu-412 and, Lys-438, (C) Lys-738 and Glu-413, (D) Glu-413,Tyr-730, and Ser-511. (E) Contact …