Extended Data Fig. 2|. Global conformational behaviour of arrestin-1 in simulation.
a, The r.m.s.d. from the inactive structure for representative simulations of arrestin-1 starting in its inactive state with: the C tail removed (green), arrestin-1 with the C tail present (grey), or arrestin-1 bound to full-length rhodopsin (blue). The simulation of arrestin-1 with its C tail removed transitions to active conformations and achieves r.m.s.d. values that match those of rhodopsin-bound active-state simulations. r.m.s.d. is computed on arrestin C-domain β-strands after alignment on the N domain. b, Mean r.m.s.d. from active and inactive structures across all six independent simulations for each condition, calculated after removing the first 500 ns of each simulation. c, We used PCA to compare the conformational states visited under the various arrestin-1 simulation conditions (see Methods; n = 8100 simulation frames as input). Each principal component corresponds to a mode of motion or variance in Cartesian coordinate space. The star on the left in each plot corresponds to the position of the active-state crystal structure, and the star on the right corresponds to the inactive-state structure. Simulations of the two crystallographic conditions separate clearly along the first principal component (PC1) and along the third principal component (PC3) but not along the second principal component (PC2). Simulations starting from the inactive state or active state with the arrestin C tail removed and no receptor present explore similar ranges of PC1 and PC2 coefficients and have some overlap in the range of PC3 coefficients. Simulations with either the receptor core or RP tail bound closely overlap with simulations performed in the presence of the full-length receptor. The x-axis is shifted to the right in the first plot in each row relative to the second and third plots in order to show the full range of values of PC1 coefficients. d, Images that show the motion of arrestin-1 along each principal component. e, Variance explained by each principal component. The cumulative distribution function (CDF) shows the variance explained by all principal components up to and including a given one.