Extended Data Fig. 7: MD simulation study and mutant study assessing the ligand binding modes.
From: Structural basis of sphingosine-1-phosphate receptor 1 activation and biased agonism
a, Key residues distance distributions with S1P (cyan), FTY720-P (green), BAF312 (purple), and ML056 (pink). Left panel, K34N-term and oxygens in the negatively-charged head groups (phosphate groups in S1P, FTY720-P, and ML056; carboxyl group in BAF312); middle panel, R1203.28 and the negatively-charged head groups; right panel, R1203.28 and N1012.60 or E1213.29. b, Representative snapshots of the key polar residues (K34N-term, N1012.60, R1203.28, and E1213.29) with the ligands during the simulations. Black dashed lines represent hydrogen bonds. c, The related position of ligands to W2696.48. FTY: FTY720-P, green color. BAF: BAF312, blue color. S1P, cyan color. d, The hydrophobic interaction between the lower part of the ligand binding pocket and the distal end of the benzyloxy oxime moiety of BAF312. e, Functional study for the F1253.33A mutation assessed by the BRET2 Gi dissociation assay. Data are presented as mean values ± SEM, n = 3-4. f, The outward displacement (arrow) of F2736.52 upon ligand binding.
