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[Preprint]. 2023 Sep 12:2023.09.12.557258. [Version 1] doi: 10.1101/2023.09.12.557258

Figure 4. HDX assays survey conformation selection among compounds in the ERK inhibitor panel.

Figure 4.

HDX measurements performed with representative inhibitors shown in Fig. 3, chosen for variations in their left-side, central scaffold, and right-side substituents. Time courses show deuterium uptake at the (A) DFG motif (peptide 161–168: LKICDFGL), (B) P+1 segment (peptide 191–198, YRAPEIML), and helix αF (peptide 203–210: YTKSIDIW). Enhanced HDX protection (strongly decreased uptake) in each segment by inhibitors #5, #6, #8 and #16 (blue) suggest properties of conformation selection for the R-state, while lower protection by inhibitors #4 and #15 (grey) suggest retention of conformational exchange. Inhibitor #1 (cyan) shows HDX properties intermediate to these two groups. HDX time courses for the full set of 17 inhibitors are shown in Suppl. Fig. S6A,B.