Assessment of mutation probabilities of KRAS G12 missense mutants and their long-timescale dynamics by atomistic molecular simulations and Markov state modeling
Fig 4
The hydrophobic interaction network of KRAS.
The interaction network is represented for the GTP-bound wild-type KRAS (A), where hydrophobic hubs are displayed as large teal spheres (except for M72 depicted as blue). The hubs are defined by the criteria that each hub displays at least three hydrophobic contacts (>10%). The hydrophobic interactions (>10%) are depicted with cylinders, where the frequency of interaction is depicted in a scale from blue and thin to red and thick for low and high frequencies, respectively. The hydrophobic residues connected to the network that can influence the switch-I and switch-II dynamics are shown in small red and blue spheres, respectively. Moreover, the hub M72 is directly part of switch-II (large blue sphere). The salt-bridge forming residues D154 and R161 are displayed as green sticks. In the 2D representation of the hydrophobic hub network (B), the hydrophobic interactions (>10%) are shown with lines, and in addition to the hubs (spheres) all the hydrophobic interacting residues to the hub network are shown (in GTP-bound wild-type). The P-loop is indicated with a dashed line.