Mutation D816V Alters the Internal Structure and Dynamics of c-KIT Receptor Cytoplasmic Region: Implications for Dimerization and Activation Mechanisms
Figure 3
Protein stability and binding free energy changes between wild-type and D816V-mutated KIT in the inactive state.
(a) Protein stability changes between wild-type and D816V-mutated KIT full-length CR: the table on the left gives the energetical contributions (in kcal/mol) computed on simulations 1 and 2 of full-length CR for wild-type (WT547-935) and mutant (MU547-935); the barplot on the right gives enthalpic (ΔH, in black), entropic (ΔTS, in dark grey) and total energy (ΔG, in light grey) changes computed from simulation 2 of WT547-935 and simulation 1 of MU547-935 (values in bold in the table). Statistical errors are given in parentheses in the table and represented as bars on the barplot. (b) Binding free energy changes of JMR and its fragments to KIT PTK between wild-type and mutant: the diagram on top represents a thermodynamic cycle picturing the dissociation of JMR from wild-type and mutated PTK; the table at the bottom gives the enthalpy (ΔΔH = ΔΔGgas+ΔΔGgb+ΔΔGsa), the entropy (ΔΔTS) and the total free energy (ΔΔG) differences (in kcal/mol), computed on the equilibrated conformations of WT547-935 and MU547-935. The different energetical contributions are defined in the Materials and Methods section.