Table 1.

Absolute binding free energy $(\mathrm{\Delta }{G}_{\mathrm{b}}^{(◦)})$ of Gleevec with Abl, c-Kit, Lck, and c-Src tyrosine kinases.^a The conformation of the A-loop in c-Src is open-form (o) or closed-form conformation (c).

site	$\mathrm{\Delta }\mathrm{\Delta }{G}_{\text{rep}}^{\text{bulk}\to \text{site}}$	$\mathrm{\Delta }\mathrm{\Delta }{G}_{\text{dis}}^{\text{bulk}\to \text{site}}$	$\mathrm{\Delta }\mathrm{\Delta }{G}_{\text{elec}}^{\text{bulk}\to \text{site}}$	$\mathrm{\Delta }\mathrm{\Delta }{G}_{\text{int}}^{\text{bulk}\to \text{site}}$	$\mathrm{\Delta }\mathrm{\Delta }{G}_{\mathrm{t}+\mathrm{r}}^{\text{bulk}\to \text{site}}$	$\mathrm{\Delta }\mathrm{\Delta }{G}_{\mathrm{c}}^{\text{bulk}\to \text{site}}$	$\mathrm{\Delta }{G}_{\mathrm{b}}^{(◦)}$	expt. b
Abl	1.2	−29.4	0.5	−27.7	5.6	11.3	−10.8	−10.8
c-Kit	7.0	−28.3	−4.7	−26.0	4.8	12.2	−9.0
Lck	0.4	−25.3	0.0	−24.9	5.2	12.4	−7.3	−8.7
c-Src(c)	0.0	−25.1	0.9	−24.2	6.3	13.3	−4.6	−6.2
c-Src(o)	4.0	−23.0	0.1	−18.9	4.6	7.5	−6.8

^aUnit in kcal/mol.

^bThe values were derived from the experimentally measured inhibitory potency of Gleevec for unphosphorylated Abl, Lck, and c-Src kinase domain, which is 0.013, 0.43, and 31.1 µM, respectively.¹⁴