Hotspot Mutations in KIT Receptor Differentially Modulate Its Allosterically Coupled Conformational Dynamics: Impact on Activation and Drug Sensitivity

doi:10.1371/journal.pcbi.1003749

Hotspot Mutations in KIT Receptor Differentially Modulate Its Allosterically Coupled Conformational Dynamics: Impact on Activation and Drug Sensitivity

Figure 4

Displacements and fluctuations of residues in KIT mutants.

(A) The RMSFs computed on the carbon and nitrogen backbone atoms over the total production simulation time of KIT mutants were compared to those in KIT^WT. (Top) RMSFs (Å) of KIT^WT [40] (graph in black) and the RMSFs difference (Δ RMSF, Å) between KIT^WT and mutants: (Middle) KIT^V560G (orange), KIT^V560D (purple), (bottom) KIT^D816V (red), KIT^D816H (green), KIT^D816Y (magenta) and KIT^D816N (blue). (B) The regions with significant average Δ RMSF values are displayed with different colors: JMR (yellow), A-loop (red), N- and C-lobe (cyan and blue) and KID (gray). The radii of the KIT cartoon representation is scaled relative to the RMSF values in KIT^WT.

doi: https://doi.org/10.1371/journal.pcbi.1003749.g004