Figure 7. The impact of hotspot mutations on structural flexibility in Ras.

(A) Sustained sidechain-sidechain contacts in the simulation of wild-type Ras•GTP. We used the network analysis tool of Vishveshwara and co-workers (Bhattacharyya et al., 2013) to analyze the molecular dynamics trajectories for Ras. Strong interactions between sidechains, as defined by Bhattacharyya et al. (2013), that are present in more than a threshold fraction of 50% of the instantaneous structures in the trajectory are identified by blue lines. These lines are drawn between the Cα atoms of the corresponding residues. (B) For simulations of Ras•GTP H27A, strong interactions are shown by blue and yellow lines. The blue lines indicate contacts that are also present in the wild-type simulation. The yellow lines indicate contacts that are unique to the mutant simulation. (C). As in (B), for Ras•GTP Q99A. (D) As in (B), for Ras•GTP L120A.

DOI: http://dx.doi.org/10.7554/eLife.27810.019

Figure 7—figure supplement 1. Residue contacts in Ras.

(A) The crystal structure of wild-type Ras•GTP with the sidechains of His 94 and Tyr 137 shown as sticks. (B–C) Shown here are 30 structures sampled from two 600 ns simulations, one for wild-type Ras (B) and one for the L120A mutant (C). The sidechains of His 94 and Tyr 137 are shown as sticks, with the Cα trace of the protein shown as a thin line.

DOI: http://dx.doi.org/10.7554/eLife.27810.020