Fig. 3. Relating ¹⁵N NMR chemical shifts of excited state of K-Ras·GTP to alternative states of K-Ras.

In all panels, data for K-Ras·GTP for WT, G12D and G12C are colored dark blue, purple and orange, respectively. a, Unsigned ¹⁵N dynamic chemical shift differences |Δϖ| between excited and ground states, obtained from CPMG and CEST experiments (Methods), plotted against the primary sequence. The dashed line is at 0.5 ppm, and the P-loop, Switch I and Switch II regions are highlighted in yellow, red and blue, respectively. b, The same results are shown as in a, but showing the effector lobe residues only. c,d, Signed ¹⁵N Δϖ values for Switch I (c) and Switch II (d) residues correlated with the equilibrium chemical shifts (Ω) and their differences observed between the ¹⁵N–¹H HSQC spectra of K-Ras·GDP and K-Ras·GTP, respectively. e,f, The corresponding correlations of Switch I (e) and Switch II (f) ¹⁵N Δϖ values with the differences between chemical shifts Ω predicted for random coil states and those observed for K-Ras·GTP. g, Depiction of the correlations between chemical shifts of the excited states of K-Ras·GTP and K-Ras·GDP for residues 1–86 with ¹⁵N |Δϖ| > 0.5 ppm. Dashed lines in c–g correspond to the diagonal with slope 1. The root-mean-square deviation and Pearson R² correlation coefficients are provided in Table 2. Errors in the measurements are smaller than the symbol sizes.

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