. 2010 Mar 3;285(18):13807–13815. doi: 10.1074/jbc.M110.109660

TABLE 1.

Imatinib binding to Abl, Src, Kit, and Lck in their inactive DFG-out conformations

Binding free energies shown in kilocalories/mol. Upper part, rigorous, MD free energy method; lower part, simpler, PB free energy method.

Method	Protein	Electrostatic term^a	Nonelectrostatic term^b	Total, ΔΔG_i	ΔΔG_expt^c	Difference, ΔΔG_ii^d
MD method	Abl	126.1/125.6^e	25.8/25.1^e	151.9/150.7^f
	Src	119.6/119.5	31.7/31.3	151.3/150.8
	Src/Abl difference^g			0.2 ± 0.6	4.6 [33]	4.4
PB method	Src/Abl difference^g	0.1 [0.2]^a	0.4/0.9^h	0.5/1.0 (1.5) ^f	4.6 [33]	4.1/3.6
	Src/Kit difference	0.6 [0.3]^a	0.7	1.3 (1.5) ^f	3.2 [81]	1.9
	Lck/Abl difference^g	−0.2 [−0.1]^a	−2.4	− 2.6 (1.5) ^f	2.1 [33]	4.7
	Lck/Kit difference	0.3 [0.0]^a	−2.3	− 2.0 (1.5) ^f	0.7 [33]	2.7

^a With MD, this is the Coulombic free energy component; with PB, it is the continuum dielectric term, which uses an ionic strength of 0.1 m monovalent salt and a protein dielectric of 4 (in square brackets, PB results with a protein dielectric of 6).

^b With MD, this is the van der Waals free energy component; with PB, it is the nonpolar term, which uses the surface area model with an atomic surface free energy of γ = 50 cal/mol/Å².

^c Total experimental binding free energy difference is shown.

^d ΔΔG_ii = ΔΔG_bind −ΔΔG_i is the conformational contribution to the binding free energy difference.

^e Results from the forward/reverse simulation (deleting/creating imatinib) are shown.

^f Uncertainty was estimated from earlier PB error analyses (49, 54, 55).

^g A negative value disfavors Abl binding.

^h A second nonpolar model was compared, the “Linear Interaction Energy” model (second value; see under “Materials and Methods”).