Extended Data Figure 9. Molecular dynamics snapshots of OR51E2.

a) Comparison of cryo-EM structure of propionate-bound OR51E2 with representative snapshots from simulations of WT OR51E2 with propionate, WT OR51E2 without ligand, and Q181^45x53D OR51E2 without ligand. Notably, OR51E2 does not transition to the inactive conformation in any of these simulations. b) Close-up views of OR51E2 binding site and ECL3 region in the cryo-EM structure and simulations. In propionate-bound MD simulations of WT OR51E2, R262^6x59 persistently forms an ionic interaction with propionate. In simulations of WT OR51E2 with propionate removed, R262^6x59 is flexible. Introduction of Asp in position 45x53 (Q181^45x53D) stabilizes R262^6x59 in an active-like state by a direct ionic interaction. c) Close-up views of OR51E2 connector region shows increased flexibility of WT OR51E2 simulated without propionate. This flexibility is decreased for the Q181^45x53D mutant. In a-c, displayed snapshots are the last 1000th ns snapshots from each simulation replicate. d and e) Molecular dynamics trajectories from representative simulations to highlight structural organization of connector region. d) Minimum distance between S111^3x40 and Y251^6x47 hydroxyl groups is comparable for Q181^45x53D and propionate-bound WT OR51E2. e) Rotamer angle of F250^6x47is comparable for Q181^45x53D and propionate-bound WT OR51E2. Simulations were performed with or without propionate over the course of 1000 ns (see Extended Data Fig. 8 for replicates of simulation trajectories). Thick traces represent smoothed values with an averaging window of 8 nanoseconds; thin traces represent unsmoothed values.