Fig. 5: Heterogeneity of the SHP2^E76K structural ensemble is supported by MD simulations and SAXS.

a Overlay of representative structures of SHP2^E76K as obtained from MD simulations. N-SH2, C-SH2, and PTP are depicted as ribbons and colored respectively in cyan, orange, and pink. The catalytic site is highlighted in red. The structures were superposed at the PTP domain. b Small-angle X-ray scattering (SAXS) curve calculated from the solution ensemble of SHP2^E76K (red line) is compared with the experimental curve (black dots), reported as raw data, and with the single-structure model by Pádua et al. (green line)⁴⁶. Radii of gyration (R_g) from the MD ensemble and from experiment are reported with black and red font, respectively. c R_g values of SHP2^E76K calculated from the ensembles of the first 500 most populated clusters via Guinier fit to calculated SAXS curves. The population of the clusters are reported in color scale. d Density map of the distance of the N-SH2 center-of-mass (d_N-SH2) from the positions respectively occupied by the N-SH2 center-of-mass either in the crystal structure of autoinhibited SHP2 (4DGP¹⁵) or in the crystal structure of open SHP2^E76K (6CRF⁴⁴). The distributions of the distance d_N-SH2 from 4DGP and from 6CRF are reported as marginal plots.