Fig. 3.

Conformation of the helical hairpin in molecular dynamics trajectories of active Sos and RasGRF1. (a) The average conformation over the six GRF trajectories is similar to that observed in the crystal structure of RasGRF1 (pink and purple cartoons, respectively). The light surface reflects the range of sampled conformations, including the average structures for 500 ps windows over all the trajectories and eight instantaneous structures representing the extremes of conformation with respect to active and inactive Sos. (Determined individually by C_α RMSD of the helical hairpin or the Rem domain with respect to comparable regions of active Sos or of inactive Sos. The instantaneous structures with the highest and lowest RMSD values for both regions with respect to both crystal structures represent the diversity of conformations achieved during the trajectories.) The dark surface surrounds the six structures that represent the average conformation of each individual simulation and thus reflects the heterogeneity among different simulations. (b) In the GRF simulations the helical hairpin is in a position more similar to active Sos (red) than inactive Sos (blue). The helical hairpin samples conformations, however, that would clash with Ras bound to the catalytic site. (c) Ras•Sos^Active simulations are more limited in the range of conformations sampled by the helical hairpin, avoiding clashes with Ras at the catalytic site.