Extended Data Fig. 10: Global prediction of E1A-Rb binding affinity.

a,b, L_p and C_eff values for E1A linkers. Boxplots: center line represents the median, lower and upper bounds represent the first and third quartiles and upper and lower whiskers extend from the top and bottom of the box by 1.4 the interquartile range. Black dots: outliers. p-values were calculated using a two-sided permutation test (10000 permutations) and the Benjamini-Hochberg correction for multiple comparisons to control the false discovery rate. ***p-value < 0.001 (detection limit of the test). N = 110: All E1A linkers, N = 24: Simulated linkers. c, C_eff as a function of linker length for 24 linkers calculated using the WLC model (L_p = 3 Å) (green dots), or L_p values from all atom simulations (L_p Sim, orange dots). Dark green/red dots: E1A_WT. d, Upper panel: E2F (blue) and LxCxE (red) motifs From E1A bound to Rb. Green sticks: core residues, blue/red sticks: variable residues. Lower panel: FoldX energy matrices with energy normalized in the range 0-2 kcal/mol. e, Fold-change in affinity (K_D,E1A (L_p = 3 Å) / K_D,E1A (L_p Sim)) using naïve versus simulated L_p. Red dot: E1A_WT. f, Predicted K_D for the E1A_E2F and E1A_LXCXE SLiMs and for the motif-linker-motif construct for 110 sequences (E1A WLC) and for 24 simulated sequences using L_p = 3 Å (K_D WLC) or sequence-specific L_p from the simulations (E1A Sim). Boxplot elements and p-values are defined as in panel a. Cyan dots: experimental value for E1A_WT. Red line: E2F2 motif affinity. g, Global Rb binding affinity (K_D,E1A) as a function of linker length for 24 sequences using the L_pSim values. K_D,E1A = K_D,E2F·K_D,LxCxE·C_eff⁻¹. The low R² value indicates that K_D,E1A is uncorrelated to linker length. Upper panel: density plot of linker length for 107 E1A linkers (three short linkers were excluded). Right panel: density plot of K_D,E1A. Red dot/line: Predicted K_D,E1A for HAdV5 (E1A_WT). Grey cross line: experimental K_D,E1A for E1A_WT.

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