Table 1.

Calculated free energy of binding ΔGbind (kcal/mol) and energy contributions to ΔGbind (kcal/mol) of WT and T315 mutant Abl kinase domains and imatinib

ContributionWTT315I
ΔEvdW−71.35 ± 0.61−67.80 ± 0.53
ΔEEL−57.44 ± 0.11−55.12 ± 0.20
ΔEMM−128.79 ± 0.11−122.92 ± 0.18
ΔGPB108.00 ± 1.20105.18 ± 1.21
ΔGNP−6.70 ± 0.03−6.18 ± 0.01
TΔS17.1017.37
ΔGbind−10.39 (−10.37)−6.55 (<−7.23)
  • NOTE: The experimental ΔGbind value (reported in parenthesis for comparison) was obtained from the corresponding experimental IC50 value (15) using the following relationship (41): ΔGbind = RTlnKdiss = RTln(IC50 + 0.50Cenz) ≅ RTlnIC50, where R is ideal gas constant, T is the temperature in Kelvin, and Cenz is the concentration of the enzyme, which is a small number after equilibration and can be omitted in most cases.